Maternal Immunization Research and Implementation Portfolio · Determine the barriers to effective tetanus toxoid implementation as a maternal vaccine, to identify necessary actions

Maternal Immunization Research

and Implementation Portfolio

Initiative for Vaccine Research (IVR) Immunization, Vaccines and Biologicals (IVB) Family, Women's and Children's Health (FWC)

Cluster

World Health Organization

Geneva, Switzerland

March 2015

Maternal Immunization Research and Implementation Portfolio -- 20 March 2015 1

Summary

The WHO Initiative for Vaccine Research (IVR) aims to provide countries and stakeholder institutions data and guidance to make evidence-based decisions about the introduction of seasonal influenza immunization programs for pregnant women. The IVR’s Maternal Immunization Team seeks to garner information from the public health community on current activities relevant to maternal immunization worldwide. Such information may include disease surveillance targeting pregnant women or young children, vaccine trials in pregnant women, vaccine demonstration projects, vaccine safety initiatives, or other activities that will strengthen the knowledge base for vaccine policies targeting pregnant women.

This portfolio will help the public health commnunity and its partners to identify relevant ongoing activities as well as potential activity gaps in need of further attention. WHO will update the portfolio regularly to track the progress of maternal immunization globally.

For this 1st version 153 stakeholders from academia, governmental organizations, academic experts, NGOs, and industry were contacted and 84 activities were submitted.

WHO is neither responsible nor accountable for activities implemented by entering entities outside specific project agreements. Through the portfolio, WHO aims to bring together experts from academia, industry, public health, donor agencies, and other stakeholder institutions to improve data sharing and to coordinate interaction in the field.

WHO would like to thank all groups that contributed to this portfolio.

Should you have any question, please write to: [email protected]


Academia, Governmental organizations, Academic experts, NGOs, and Industry

Implementing Organization Activity Name Agence de Médecine Préventive (AMP) Evidence generation, policy development

American College of Obstetricians and Gynegologists

Training and tools

Better Outcomes Registry & Network (BORN) Ontario and the Institute for Clinical Evaluative Sciences (ICES)

Evidence generation

Boston University School of Public Health Evidence generation

Brighton Collaboration Foundation Regulatory support, training and tools, global collaboration

Bureau of Epidemiology, Department of Disease Control, Ministry of Public Health, Thailand

Evidence generation

Canadian Pediatric Society Policy development, training and tools

Canadian Center for Vaccinology Evidence generation

Case Western Reserve University Evidence generation

CDC/ Clinical Immunization Safety Assessment (CISA) Project

Evidence generation

CDC/Vaccine Adverse Event Reporting System (VAERS)

Evidence generation

CDC/Vaccine Safety Datalink (VSD) Project Evidence generation

Center for infectious disease research, Zambia Evidence generation

Centre for Respiratory Diseases and Meningitis (CRDM), National Institute for Communicable Diseases (NICD) and Respiratory and Meningeal Pathogens Research Unit University of the Witwatersrand

Evidence generation

Communicable Disease Control Directorate, Western Australia Department of Health

Evidence generation

DCVRN Regulatory support

Department of Disease Control, Ministry of Public Health, Thailand

Feasibility and best practice


Implementing Organization Activity Name Duke University Evidence generation

Emmes Evidence generation

Emory University Evidence generation, policy development, feasibility and best practice, training and tools

Emory University, Aga Khan University Evidence generation, policy development, global collaboration

Emory University, Johns Hopkins University Evidence generation, Policy development, feasibility and best practice, training and tools

Emory University, Universidad del Valle de Guatemala

Evidence generation, policy development, global collaboration

EPI program,, Mnistry of Public Health, Thailand Policy development, feasibility and best practice

FDA Evidence generation, feasibility and best practice, regulatory support, training and tools

FDA and CMS Evidence generation, feasibility and best practice, regulatory support

FDA Sentinel Feasibility and best practice, regulatory support

FRED HUTCHINSON CANCER RESEARCH CENTER Evidence generation

GlaxoSmithKline Vaccines (formerly Novartis Vaccines)

Evidence generation

Global coordination through a public health institution (FISABIO) in Valencia, Spain

Evidence generation, global collaboration

Guangzhou Center for Disease Control and Prevention

Evidence generation

Hellenic Center for Disease Control and Prevention, University of Athens, Athens, Greece

Policy development, training and tools, ethics and liability issues, global collaboration

Johns Hopkins Bloomberg School of Public Health Evidence generation

Karolinska Institutet, Stockholm, Sweden Evidence generation

Levin and Morgan Health Training and tools

London School of Hygiene/ Paul-Ehrlich-Institut Evidence generation, regulatory support, global collaboration

Massachusetts General Hospital Evidence generation, feasibility and best practice

McMaster University Evidence generation

Medicines and Healthcare products Regulatory Agency (MHRA)

Evidence generation


Implementing Organization Activity Name Menzies School of Health Research Evidence generation

MRC Unit, The Gambia Evidence generation, policy development, global collaboration

NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

Evidence generation

National Institute of Health Clinicla Center Evidence generation

National Institute of Public Health and the environment in close cooperation with midwives and departments of obstetrics

Evidence generation, feasibility and best practice

National Vaccine Advisory Committee, National Vaccine Program Office, DHHS, US

Policy development

National Vaccine Program Office Evidence generation, policy development

National Vaccine Program Office, Office of the Assistant Secretary for Health, Department of Health and Human Services, US

Evidence generation

Naval Health Research Center, San Diego, CA, USA Evidence generation

NIH Evidence generation

NIH/BMGF Global collaboration

Novavax, Inc. Evidence generation, feasibility and best practice, training and tools, ethics and liability issues, global collaboration

Ohio State University Evidence generation

PATH Evidence generation, Policy development, Feasibility and best practice

PATH and the University of Malawi Evidence generation, Feasibility and best practice, Training and tools

PATH and WHO Initiative for Vaccine Research Evidence generation, Policy development ,Feasibility and best practice, Regulatory support

PHE Evidence generation, Policy development ,Feasibility and best practice

PHE, MHRA Evidence generation, Policy development, Feasibility and best practice

PIVI Partner Country's Ministries of Health, CDC, Task Force for Global Health, Partner organizations

Evidence generation, Policy development, Feasibility and best practice, Training and tools, Global collaboration

RHI Evidence generation, policy development, feasibility and best practice, global collaboration

Rhode Island Hospital Evidence generation, training and tools


Implementing Organization Activity Name

Rutgers University Evidence generation

Statens Serum Institut, Copenhagen. Evidence generation

Swiss Tropical and Public Health Institute Evidence generation, feasibility and best practice, training and tools

Task Force for Global Health, CDC (NCIRD, GID) Evidence generation, policy development, feasibility and best practice

The American College of Obstetricians and Gynecologists (ACOG)

Training and tools

The Ohio State University Wexner Medical Center Evidence generation

TRELLIS BIOSCIENCE, LLC Evidence generation

Tulane University of Louisiana Evidence generation, global collaboration

University of Massachusetts Medical School Worcester

Evidence generation

University of North Carolina Chapel Hill Evidence generation

University Hospitals of Geneva, Switzerland Evidence generation

University of Antwerp Evidence generation, regulatory support, global collaboration

University of Auckland Evidence generation

University of Baltimore Maryland Evidence generation

University of Siena, Italy; Novartis Vaccines Academy

Evidence generation, policy development, feasibility and best practice, training and tools, global collaboration

University of Texas Southwestern Medical Center Evidence generation, feasibility and best practice

University of Washington Evidence generation, training and tools, global collaboration

US Centers for Disease Control and Prevention; BMG Foundation

Policy development

US FDA Regulatory support

VIRTU Evidence generation

WESTAT Evidence generation

WHO Evidence generation

WHO and PATH Policy development

Wits Health Consortium Evidence generation


Maternal Immunization Research and Implementation Portfolio

Table of contents

8

59

148

152

159

163

168

Cross-cutting activities

Evidence generation

Policy development

Feasibility and best practice

Regulatory support

Training and Tools

Ethics and liability issues

Global collaboration 169


Activity Identification Evidence generation, policy development, feasibility and best practice, regulatory support Activity title Maternal influenza immunization project - country case

studies Activity objective Assess current experience with maternal immunization programs

in developing countries Activity description

To further identify and address some of the obstacles to implementing seasonal influenza immunization programs for pregnant women, PATH and WHO are working together on a new project called the Maternal Influenza Immunization Project (MIIP). Funded by the Bill and Melinda Gates Foundation, this three-year project aims to solve key barriers, including gaps in the scientific evidence, regulatory hurdles, implementation issues, and influenza vaccine supply concerns. One main objective of the project is to explore the feasibility of introducing and/or integrating maternal influenza vaccination with existing health services in low- and middle-income countries. Through our research, we aim to (1) identify policy, program and infrastructure requirements for introducing and/or integrating maternal influenza immunization; (2) generate and verify country-specific evidence on sociocultural determinants of anticipated maternal vaccine acceptance, and (3) raise awareness of key global decision-makers of the feasibility of introducing and/or integrating maternal influenza vaccine in low- and middle-income countries.

Expected output Study reports and publications expected Project lead Jessica Fleming, Niranjan Bhat, Kathy Neuzil, Justin Ortiz Type of activity Formative research Location El Salvador,Mali Activity start 1/15/2015 Activity end 1/31/2017 Implementing organization

PATH and WHO Initiative for Vaccine Research

Activity contact name

Niranjan Bhat

Source of funding Bill & Melinda Gates Foundation


Activity Identification Evidence generation, policy development, feasibility and best practice, training and tools, global collaboration

Activity title Dissertation for master of science in vaccinology and clincial development

Activity objective Review the successes of the maternal tetanus toxoid immunization program established in sub Saharan Africa and Asia and its contribution towards global maternal and neonatal tetanus elimination. Determine the barriers to effective tetanus toxoid implementation as a maternal vaccine, to identify necessary actions for program strengthening and new vaccine introduction.Review the diseases and the corresponding vaccines recommended by the CDC and WHO for use in pregnancy, including vaccines in development.

Activity description

Focusing on sub Saharan Africa and Asia, we conducted a literature review of the maternal vaccines currently available and those in development as well as the achievements of the tetanus toxoid vaccination (TTV) program in antenatal care (ANC) and the use of TTV for maternal and neonatal tetanus elimination (MNTE). An assessment of the barriers to utilization of maternal immunization through the provision of TTV in ANC was also conducted to identify the strengths and weaknesses of service delivery. This was done through a literature review (including country EPI multi year plans)and a survey of health care providers. Barriers were classified into Health System, Health Care Provider and Patient level barriers. Health care providers at district level were surveyed in Malawi and Key Opinion Leaders from The Gambia, Uganda, Malawi, South Africa, Bangladesh and China with experience in their national EPI were interviewed. Multi Year Plans from Cambodia, Pakistan, Angola and Ethiopia were also assessed.

Expected output Contribute to developing policy on maternal immunization and identifying gaps in vaccine implementation for pregnant women

Project lead Jayani Pathirana, Steven Black

Type of activity Literature Review on maternal vaccines on the market and in development with review of disease epidemiology, vaccine impact and maternal vaccination strategySurvey of health care providers in Malawi on the barriers they experience in immunizing pregnant womenInterview of key opinion leaders on the achievements and barriers of their EPI in immunizing pregnant women from African and Asian countries

Location All countries

Activity start 9/1/2013 Activity end 11/17/2014


Implementing organization

University of Siena, Italy; Novartis Vaccines Academy


Jayani Pathirana

Source of funding Novartis Vaccines Academy Scholarship


Activity Identification Evidence generation, policy development, feasibility and best practice, training and tools global collaboration

Activity title PIVI Maternal immunization projects

Activity objective PIVI plans to conduct evaluations designed to contribute to both country-level decisions and future GAVI investment strategies for maternal immunization with influenza vaccine, and eventually build sustainable maternal immunization approaches in partner countries.


The objective of PIVI impact evaluations will be to measure two different types of impact of influenza vaccination during pregnancy: reduction in the risk of influenza illnesses in mother and infant and reduction in the risk of adverse birth outcomes. As part of programmatic evaluations, PIVI will also assist Ministries of Health in conducting New Vaccine Post Introduction Evaluations and Vaccine Program Cost Assessments.

ExceptExpected Country Reports, Peer review publications, website , partner meeting presentations

Project lead Country's Minstries of Health

Type of activity Vaccine effectiveness (i.e. health impact outcomes), economic analyses, programmatic outcomes

Location Armenia,Lao People's Democratic Republic,Morocco,Nicaragua

Activity start 1/1/2012 Activity end


PIVI Partner Country's Ministries of Health, CDC, Task Force for Global Health, Partner organizations


Sara Mirza, Joseph Bresee

Source of funding CDC, Bill and Melinda Gates Foundation, PIVI partners


Activity Identification Feasibility and best practice, regulatory support

Activity title Influenza vaccines and pregnancy outcomes

Activity objective


Establish the methodological framework for study pregnancy outcomes such as spontaneous abortion in FDA's Sentinel system. Using a case-time-control design, examine the risk of spontaneous abortion after trivalent influenza vaccination.

Expected output Final Report and publication

Project lead Alison Kawai

Type of activity Vaccine Safety

Location United States of America



FDA


michael nguyen

Source of funding US Department of Health and Human Services


Activity Identification Evidence generation, global collaboration

Activity title Global influenza hospital surveillance network

Activity objective To estimate the burden of severe influenza (requiring hospitalization), related flu strains and flu vaccine effectiveness (when coverage is sufficient) in several sites worldwide. This activity focuses on the general population and includes pregnant women and children.


Hospital network (about 35 hospitals in 7 countries to date). All subsequent individual with ILI

Expected output Yearly meeting + scientific papers

Project lead Clotidle El Guerche Seblain (Project lead)

Type of activity Burden of severe flu, relative risk of severe flu in specific populations (incl pregnant women), vaccine effectiveness, economic impact,...




Global coordination through a public health institution (FISABIO) in Valencia, Spain


Clotilde El Guerche Seblain

Source of funding Sanofi Pasteur + local budgets


Activity Identification Evidence generation, policy development, feasibility and best practice Activity title Partnership for influenza vaccine introduction (PIVI) Activity objective Assist low- and middle-income countries to introduce or expand

seasonal influenza vaccination programs to protect high-risk individuals as defined by WHO SAGE (particularly pregnant women) from disease and death associated with seasonal influenza


Provide donated seasonal influenza vaccine to developing countries as well as technical assistance, monitoring and evaluation.

Expected output Publications about activities Project lead Alan Hinman Type of activity health and programmatic impact of maternal influenza

immunization Location Armenia,Lao People's Democratic Republic,Morocco,Nicaragua Activity start 8/22/2013 Activity end 2/28/2015 Implementing organization

Task Force for Global Health, Centers for Disease Control and Prevention


Alan Hinman

Source of funding Bill & Melinda Gates Foundation, Centers for Disease Control and

Prevention


Activity Identification Evidence generation, policy development Activity title Overcoming impediments to development of vaccines for

pregnant women Activity objective To develop recommendations to overcome barriers to

development of new vaccines to prevent disease in pregnant women and/or their children


I am Chairman of the National Vaccine Advisory Committee (NVAC) in the United States. The NVAC will be reviewing this subject over the next year.

Expected output Publication with recommendations to overcome barriers Project lead Walter Orenstein as Chair - Rich Beigi and Saad Omer are the co-

chairs of our Maternal Immunization Working Group on NVAC Type of activity Broad analysis of data Location United States of America Activity start 1/1/2014 Activity end 12/31/2016 Implementing organization

National Vaccine Program Office


Bruce Gellin

Source of funding US Government


Activity Identification Evidence generation, feasibility and best practice, training and tools Activity title Develop a generic protocol to examine prospects and

problems for vaccinating pregnant women for influenza in low-resource countries

Activity objective Develop generic protocol, including study design and instruments,

to identify social and cultural determinants of influenza vaccination coverage with reference to community demand, interest, hesitancy and barriers.


Based on a cultural epidemiological framework for study of community determinants of vaccine coverage, a generic protocol is being developed to indicate motivating interests, study aims, characteristics of prospective low- and middle-income country study sites, survey instruments, options for study designs and strategies for analysis and interpretation of findings from implementation of the protocol. In addition to a generic protocol for operational use, a design for a validation study will be suggested to test the impact of this approach for community assessment on vaccination coverage of pregnant women for influenza. A telephone or video conference with potential partners is being organized in cooperation with WHO IVR, and with their guidance and support, to assess interest and to motivate local operational adaptation and implementation of the protocol, including consideration of developing a validation study.

Expected output A report outlining key elements of the generic protocol, including

an approach to local adaptation and prospects for implementation at a specified project site initially, and subsequently at other sites.

Project lead Mitchell G. Weiss Type of activity Development of a protocol for study of community determinants

vaccine coverage Location India,Kenya,Singapore,Thailand Activity start 1/1/2015 Activity end 4/30/2015 Implementing organization

Swiss Tropical and Public Health Institute


Mitchell G. Weiss

Source of funding WHO IVR


Activity Identification Evidence generation, feasibility and best practice, training and tools

Activity title Piloting the WHO flu tool in Malawi

Activity objective Determine the strengths, weaknesses and opportunities to improve the WHO FluTool and collect cost data on a prospective maternal influenza immunization program in Malawi.


Collect cost data for existing vaccination activities in Malawi and estimate the costs of a maternal influenza program.

Expected output Costing report, report discussing use of the FluTool

Project lead Clint Pecenka, Spy Munthali

Type of activity Costing study, pilot study

Location Malawi



PATH and the University of Malawi


Clint Pecenka

Source of funding


Activity Identification Evidence generation, feasibility and best practice Activity title Trial maternal pertussis immunisation in the Netherlands Activity objective To assess the added value of maternal immunisation to improve

the control of pertussis, particularly severe disease in infants too young to be (fully) vaccinated themselves.


A study with two arms:1. Maternal DTaP-IPV at 28-32 weeks of gestation; DTaP-IPV for fathers directly after birth of their baby; first infant vaccination postponed to 3 months of age (instead of the regular 2 months)2. DTaP-IPV for both fathers and mothers directly after birth of their baby; first infant vaccination postponed to 3 months of age (instead of the regular 2 months)Assessment of immunogenicity (anti-PT infant at 2 and 3 months of age; response to further infant doses)

Expected output peer reviewed publication Project lead Nynke Rots Type of activity immunogenicity trial Location Netherlands Activity start 1/1/2014 Activity end 8/1/2017 Implementing organization

National Institute of Public Health and the environment in close cooperation with midwives and departments of obstetrics


Nynke Rots

Source of funding Ministry of Health, The Hague, Netherlands


Activity Identification Evidence generation, regulatory support, global collaboration Activity title Evaluation of maternal immunisation safety Activity objective Continous regulatory evaluation of safety relavnt data (AEFI

assessment, regulatory assessment and risk management as an NCA)Systematic literature review of safety of vaccines during pregnancy


I have chaired a GAGVS subgroup summarising the safety of maternal immunisations (Keller-Stanislawski B, Englund JA, Kang G, Keller-Stanislawski B, Englund JA, Kang G, Mangtani P, Neuzil K, Nohynek H, Pless R, Lambach P, Zuber P. Safety of immunization during pregnancy: A review of the evidence of selected inactivated and live attenuated vaccines. Vaccine. 2014 Oct 5;32(52):7057-7064. doi: 10.1016/j.vaccine.2014.09.052. [Epub ahead of print] Review)Currently we are conducting a systematic reveiw on the safety of inadvertant rubella vaccination during pregnancy together with colleagues of the london School of Hygiene

Expected output Draft puplication in preparation Project lead Magtani Punam/ London School of Hygiene Type of activity Vaccine safety Location All countries Activity start 11/1/2013 Activity end 2/27/2015 Implementing organization

London School of Hygiene/ Paul-Ehrlich-Institut


Punam Magtani, Brigitte keller-Stanislawski

Source of funding WHO and Paul-Ehrlich-Institut


Activity Identification Regulatory support, ethics and liability issues, global collaboration

Activity title Liability considerations (real and perceived) related to maternal immunization

Activity objective Describe liability implications if maternal influenza immunization were to receive third-party investment leading to use of vaccine by pregnant women in low-resource countries; suggest potential mechanisms or processes that could ameliorate liability concerns in low resource settings.


Analyse legal and regulatory barriers to increased maternal influenza immunization efforts including product labeling standards, ""off-label"" use and promotion, regulatory approval mechanisms, product liability regimes, and anti-bribery laws.

Expected output Report

Project lead Sam Halabi

Type of activity Analysis of legal and regulatory conditions




Not applicable


Sam Halabi

Source of funding WHO


Activity Identification Evidence generation, policy development, feasibility and best practice Activity title Maternal influenza immunization: building an

immunization platform in conjunction with antenatal care in low and middle-income countries

Activity objective Assess current experience with maternal immunization programs

in developing countries. Activity description

Conducting formative research in 3 countries to identify information needs and generate evidence for decision-making and operational planning relevant to potential maternal influenza vaccine introduction in low income countries.Specific objective so the studies include:1. To describe the knowledge, attitudes and practices of pregnant women, their social networks, and health workers concerning influenza and maternal vaccination.2. To describe the delivery system for maternal vaccines and identify system and community-level factors that enable or hinder effective delivery of vaccination services targeting pregnant women. 3. To identify program, infrastructure, and training requirements for maternal influenza vaccine introduction and integration with antenatal care services based on the experience of the maternal tetanus program. 4. To assess the adequacy of the Health Management Information System to capture coverage and adverse events data associated with maternal vaccination. 5. To describe the vaccine and maternal/child health policy environment for maternal vaccination in Malawi.

Expected output Country reports, dissemination workshops with key country

stakeholders, peer-reviewed manuscript Project lead Justin Ortiz (WHO); Jessica Fleming leading activity for PATH Type of activity Formative research Location El Salvador,Lao People's Democratic Republic,Malawi Activity start 1/1/2014 Activity end 12/31/2016 Implementing organization

PATH


Jessica Fleming

Source of funding Bill & Melinda Gates Foundation (through WHO)


Activity Identification Feasibility and best practice, regulatory support, training and tools Activity title Two-dimensional scan statistics for assessing vaccine

safety in Pregnancy (PRISM) Activity objective Activity description

Methods project including two simulation studies to:1.Evaluate the performance of (1-dimensional) temporal scan statistics under various scenarios and2.Evaluate the performance of a 2-dimensional temporal scan statistic under alternative assumptions about pregnancy outcomes

Expected output Final report and publication Project lead Lingling Li, PhD Type of activity Vaccine safety Location United States of America Activity start 11/14/2014 Activity end Implementing organization

FDA


Michael Nguyen



Activity Identification Evidence generation,Regulatory support

Activity title Gardasil 9 pregnancy outcomes study

Activity objective


Evaluate the risk of pregnancy outcomes after Gardasil 9 vaccination in the United States.

Expected output Final Report and publication

Project lead Alison Kawai

Type of activity Vaccine Safety


Activity start Activity end


FDA


michael nguyen



Activity Identification Policy development, training and tools Activity title Canandian Paediatric Soc practice point on prevention of

influenza in 0 to 6 month olds - major focus is on immunization in pregnancy.

Activity objective Change practice of family physicians and obstetricians etc Activity description

Practice Point developed , published, now entering knowledge translation phaseNB all pediatric residents writing their Royal College fellowship exams focus on CPS practice points and statements as will be on national exams.

Expected output http://www.cps.ca/en/documents/position/influenza-vaccine-in-

pregnancy Project lead Noni MacDonald Type of activity Development of Practice Point by Can Paed Soc Infectious Dis and

Immunization CommitteeWork now on dissemination and education

Location Canada Activity start 1/1/2014 Activity end 2/1/2016 Implementing organization

Canandian Pediatric Society


Source of funding


Activity Identification Evidence generation, feasibility and best practice, training and tools, ethics and liability issues, global collaboration Activity title Maternal immunization with an RSV-F nanoparticle vaccine Activity objective License a vaccine for the prevention of severe RSV disease in

infants, 0 - 6 months of age (minimum, 0 - 3 months of age) Activity description

Integrated global clinical development plan aimed at demonstratiing the effectiveness of Novavax' RSV-F nanoparticle vaccine in the prevention of severe RSV disease in infants, 0 - 6 months of age (minimum, 0 - 3 months of age)

Expected output Publication of clinical trial results through a combination of press

releases, journal articles and scientific presentations Project lead Allison August, Lead Maternal Immunization Development Team,

Novavax, Inc. Type of activity Learn background epidemiology in different regions around the

world in pregnant women and newborns, analyze the efficacy of vaccine to reduce incidence of disease in those populations

Location All countries Activity start 1/1/2010 Activity end Implementing organization

Novavax, Inc.


Allison August, M.D.

Source of funding PATH, self-funding


Activity Identification Evidence generation, policy development, feasibility and best practice Activity title Portfolio of programme evaluation relating to the

introduction of immunisation against pertussis for pregnant women from October 2012 as part of a pertussis outbreak response

Activity objective predominantly programme evaluation Activity description

Routine collection of coverage data for women delivering each month.Ongoing collection of routine surveillance data (laboratory confirmed cases, hospitalisations, clinical notifications, deaths).Clinical service evaluation to monitor the immune responses of UK infants to their primary vaccination following national introduction of pertussis vaccination in pregnancy (code: iMAP1);Survey of attitudes of pregnant women and women with children under 2 years towards immunisation in pregnancy;Annual survey of attitudes of parents/guardians of young children

Expected output See below for list Project lead iMAP Principal Investigator - Professor Liz Miller Type of activity Routine publication of coverage data

https://www.gov.uk/government/publications/pertussis-immunisation-in-pregnancy-vaccine-coverage-estimates-in-england-october-2013-to-march-2014 ;Routine publication of surveillance data https://www.gov.uk/government/collections/health-protection-report-latest-infection-reports#immunisation Peer reviewed publications: • Dabrera G, Amirthalingam G, Andrews N, Campbell H, Ribeiro S, Kara E, Fry NK, et al. A case-control study to estimate the effectiveness of maternal pertussis vaccination in protecting newborn infants in England and Wales,2012-2013. Clin Infect Dis, 2014; Oct 19. pii: ciu821.• G Amirthalingam, N Andrews, H Campbell, S Ribeiro, E Kara, K Donegan, N K Fry, E Miller, M Ramsay. Effectiveness of maternal pertussis vaccination in England: an observational study. The Lancet, 2014.• iMAP1 (pending)• attitudinal survey (pending)iMAP2 http://public.ukcrn.org.uk/Search/Portfolio.aspx?titleAcro=imap2&SearchType=Any Vaccine safety study Donegan K et al Safety of pertussis vaccination in pregnant women in UK: observational study. BMJ 2014 http://www.bmj.com/content/349/bmj.g4219

Location United Kingdom of Great Britain and Northern Ireland Activity start 10/1/2012 Activity end Implementing PHE, MHRA


organization Activity contact name

Helen Campbell

Source of funding


Activity Identification Evidence generation, policy development Activity title Establishment and Strengthening of National immunization

Technical Advisory Groups (NITAGs) Activity objective To support decision-making by facilitating the use of local and

global evidence in the formulation of immunization policies and strategies using internationally accepted methodologies.


SIVAC supports NITAGs to formulate and issue scientific and evidence-informed recommendations to health authorities based on local and global evidence, that they gather, analyze and interpret. their scope covers all vaccines issues in all ages, thus, maternal and child health. Support is offered to NITAG members and executive secretariats, through trainings and capacity building activities, including suport to working groups working on specific issues requiring external technical support.

Expected output Recommendations issued, implemented by MoH Project lead Dr Alex Adjagba Type of activity Trainings on evidence analysis, health economics, socio-

anthropology in relation to vaccines and immunization Location All countries Activity start 4/1/2008 Activity end 8/31/2017 Implementing organization

Agence de Médecine Préventive


Dr Alex Adjagba

Source of funding Bill and Melinda Gates Foundation and Gavi the Vaccine Alliance

(from 2014)


Activity Identification Evidence generation, policy development, feasibility and best practice Activity title Seasonal influenza vaccination in pregnant women Activity objective Routine enhanced surveillance Activity description

Seasonal collection of coverage data for women delivering each month.Seasonal collection of routine surveillance dataMBRRACE confidential enquiry into maternal mortality and morbidity: Saving Lives, Improving Mothers’ CareSurvey of attitudes of pregnant women and women with children under 2 years towards immunisation in pregnancy;Annual survey of attitudes of parents/guardians of young children

Expected output see below - routine surveillance data, MBRRACE Report, peer-

reviewed publications Project lead Type of activity various with related

publicationshttps://www.npeu.ox.ac.uk/mbrrace-uk/reportshttps://www.gov.uk/government/publications/annual-flu-reportshttps://www.gov.uk/government/collections/winter-health-watch

Location United Kingdom of Great Britain and Northern Ireland Activity start Activity end Implementing organization

PHE


Richard Pebody

Source of funding


Activity Identification Evidence generation, policy development, feasibility and best practice, global collaboration Activity title 1. World Health Organisation (WHO) strategic advisory

group of experts on immunisation, reporting to director general of WHO; 2. Maternal immunisation for RSV. 3. Acceptability and feasibility of maternal vaccines.

Activity objective 1. Provide leadership, technical advice, expertise and

development of strategic direction for WHO regarding maternal and paediatric vaccination.2. Implementation of PATH/NOVOVAX developed Research Protocol investigation maternal RSV vaccination, with active and passive surveillance for infant LRTI and RSV.3. Quantify and qualify feasibility and acceptability of the implementation of routine and research vaccines for women and children in City of Johannessburg and North West Province, South Africa.


1) • Chair, Regional Technical Advisory Forum on Vaccines and Immunization (TFI) AFRO Region, 2013 to date.• Observer, WHO’s Strategic Advisory Group of Experts on Immunisation (SAGE), responsible for making recommendations to the Director General of WHO on all matters to do with Vaccines and immunisation. This expert committee is one of WHO’s most important and effective committees with oversight of all vaccine related global recommendations issued by WHO. Member from 2004 -2013. Chair from 2008 to 2013. • Chair, WHO PATH Maternal Influenza Immunization Project Technical Advisory Group, 2013 to date.• Chair of International Health Regulations (IHR) Emergency Committee on Polio, 2014 to date.• Member, SAGE Working Group on Ebola, 2014 to date.• Chairperson of SAGE Use of Vaccines in Humanitarian Emergencies Working Group, 2011 to date. • Member of SAGE Measles and Rubella Working Group and previous Chair of Rubella Working group, 2009 to date.• Member of Polio Vaccine Research Scientific Advisory Committee, 2013 to date.• Member of Decade of Vaccine International Advisory Committee, 2010 to date.• Member of Global Advisory Committee on Vaccine Safety, 2009 to date. • Member, RSV Vaccine Development Technical Advisory Group, 2015 to date.• Member of Scientific Organizing Committee of WHO Global Vaccine and Immunization Research Forum (GVRIF), 2014 to 2016.• Member of WHO Department of Reproductive Health and Research Scientific and Technical Advisory Group (STAG), 2013 to date.• Member of the Ebola Vaccine Access and Financing Group, 2014 to date.• Member of the Global Strategy for Sexually Transmitted Infections Group, 2013 to date.Publication: Rees H, Madhi S. Will the decade of vaccines mean business as usual? The Lancet. 2011 //;378(9789):382-5. IF=36.427, CI=5.2. Research protocol implementation at Shandukani Research Centre.3. Qualitative study through individual consultations and workshops, including clients and health care workers, establishing acceptability and feasibility of maternal and paediatric vaccinations (routine and


research) in a South African population. Expected output 1. Meeting report; WHO bulletin; Guideline Recommendations.2.

Publication and dissemination of findings through PATH/NOVOVAX 3. Publication and report to stakeholders (including Department of Health and Research bodies).

Project lead 1. Professor Vera Helen Rees. 2. Dr Lee Fairlie (RHI) lead by

PATH/NOVOVAX 3. Dr Saiqa Mullick Type of activity 1. Strategy development.2. Clinical Trial 3. Implementation

science research Location South Africa Activity start 1/1/2004 Activity end 3/9/2015 Implementing organization

RHI


Vera Helen Rees

Source of funding Numerous including WHO; USAID/PEPFAR; PATH/NOVOVAX


Activity Identification Training and tools, global collaboration Activity title International core Activity objective To facilitate research to address cutting-edge global HIV issues. Activity description

We will emphasize implementation science in pilot awards, and promote research on combination HIV prevention, chronic treatment, and vulnerable populations. We will establish a new sub-Core on Economic Evaluation, partnering with the Bill and Melinda Gates Foundation to determine sustainability and cost considerations for implementation. We will extend collaborations from mature partners (Kenya, Peru) to new partners including regional neighbor countries; in addition, we will leverage activities of relevant UW DGH Centers (HAI, l-TECH, Global WACh) and Seattle global health organizations (BMGF, PATH) to facilitate research by CFAR investigators. We will provide infrastructure and co-develop training for international sites

Expected output Project lead King K. Holmes Type of activity Location All countries Activity start Activity end Implementing organization

University of Washington


Source of funding NIH/NIAID


Activity Identification Evidence generation, policy development, feasibility and best practice, regulatory support, global collaboration Activity title Clinical trial aim to search for the measles vaccine virus

excretion in breast milk of breastfeeding women after postpartum vaccination with a combined measles-mumps-rubella (MMR) vaccine.

Activity objective In order to assess the safety of breastfed infants after their

mother’s postpartum immunization with a combined measles-mumps-rubella (MMR) vaccine, the purpose of this study is to investigate whether measles vaccine strain is excreted in breast milk of breastfeeding women with negative rubella and measles serologies.


This is a multicentre prospective study, to evaluate the safety of infant from 50 breastfeeding women, analyzable for primary endpoint, after postpartum immunization with MMR vaccine.Women meeting all the inclusion criteria and none of the exclusion criteria will be vaccinated in post partum and before the exit of the maternity at day 0. Each woman will have a blood draw at day 0 and breast milk samples as well as urine samples at the hospital at day 0 before vaccination. Each included woman will also provide breast milk and urine home samples at days 7, 11 and 14 after vaccination. Women will then be followed and vaccinated 8 weeks after the first vaccination. Each infant will be followed during 8 weeks. If Infant and/or mother develop(s) suspected measles symptom(s), they will be evaluated by a study physician as soon as possible, preferably within 24 to 72 hours of acute measles symptom(s) onset.

Expected output Publication ; Considering stopping production of monovalent

vaccine against rubella, the results of this trial are needed to adapt the French vaccine recommendations in post-partum period.

Project lead Pr. Odile Launay Type of activity Vaccine safety, prevention Location Belgium, France Activity start 1/21/2015 Activity end Implementing organization


Odile Launay


Source of funding French ""programme hospitalier de recherche clinique (PHRC)"" and ""Institut national de la santé et de la recherche médicale (INSERM)""


Activity Identification Evidence generation, global collaboration Activity title G-grippenet - Application of GrippeNet, a web-based

project that monitors the activity of influenza-like-illness (ILI) with the aid of volunteers, to the specific population of French pregnant women.

Activity objective To estimate (i) the incidence of ILI, (ii) the vaccine coverage and

(iii) the field effectiveness of the seasonal influenza vaccine in French pregnant women.


GrippeNet is part of the European network Influenzanet, leaning on Internet and based on the voluntary participation of the citizens by suggesting them answering a weekly questionnaire on their health towards influenza (symptoms, vaccinal status, etc.).G grippenet is dedicated to the pregnant women. Women will be followed during their pregnancy and until delivery. This project will allow to identify barriers and predictors of vaccination in this population to target strategies to improve influenza immunization coverage.Every pregnant woman living in metropolitan France during the 2014/2015 Influenza season can be included regardless of the immunization status.

Expected output All results on participation, vaccination status are updated daily

and available online at www.grippenet.fr. More detailed results will be published at the end of the study.

Project lead Solen Kernéis Type of activity Analysis of disease incidence, vaccine effectiveness Location France Activity start 11/19/2014 Activity end Implementing organization


Solen Kernéis

Source of funding European project FP7-Influenzanet project ; French Sentinelles

network « Réseau Sentinelles » (Inserm/Université Pierre et Marie Curie) ; « Société de Pathologie Infectieuse de Langue Française (SPILF) »


Activity Identification Evidence generation, feasibility and best practice Activity title Laser-based powder vaccome delivery for improved

newborn immunization Activity objective Enhancing newborn vaccine immunogenicity is the key to reduce

early infection-associated high morbidity and mortality in newborns


laser-based powder delivery (LPD) in combination with a clinical monophosphoryl lipid A (MPL) adjuvant (MPL/LPD) is proposed for improved newborn immunization. Laser generates self-renewable microchannels in the skin surface. After topical application of powder vaccine/MPL-coated array patches, vaccine/MPL can be efficiently deposited into these microchannels, dissolved in situ, and efficiently taken up by or activate skin antigen-presenting cells (APCs). MPL/LPD-based immunization is expected to profoundly improve newborn vaccine immunogenicity

Expected output publication Project lead CHEN, XINYUAN Type of activity veccine effectiveness Location All countries Activity start 6/1/2013 Activity end 5/31/2015 Implementing organization

Massachusetts General Hospital


Christopher E. Taylor



Activity Identification Evidence generation, global collaboration

Activity title

Activity objective improving the immunogenicity and efficacy of IPV and other vaccines


There are number of potential approaches for improving the immunogenicity and efficacy of IPV and other vaccines, including alternate delivery routes (e.g., intradermal or sublingual) and the use of nano-scale delivery systems. Our own nano- and micro-scale technology vaccine delivery to enhance the immunogenicity and efficacy of multiple vaccines by different routes of immunization. For this project, our primary focus will be on the use of nano-scale carriers to facilitate intradermal and sublingual delivery of IPV.

Expected output publication

Project lead CLEMENTS, JOHN D

Type of activity vaccine effectiveness




Tulane University of Louisiana


Eun-Chung Park

Source of funding nih/niaid


Activity Identification Evidence generation,Policy development,Global collaboration

Activity title Evaluation of Tdap in pregnancy to prevent infant Pertussis

Activity objective Primary objective:To determine antibody responses to Tdap vaccine in pregnant women immunized between 27-36 weeks gestation, as well as antibody responses to routine childhood DTwP vaccines in their infants.Secondary objective: To determine if maternal vaccination with Tdap administered during the third trimester of pregnancy (Tdap vaccination at 27-36 weeks gestation) leads to a decreased incidence of laboratory-confirmed pertussis in infants younger than 6 months of age.


The project is a randomized, double-blind, controlled, vaccine trial to evaluate the immunogenicity of maternal Tdap immunization. The vaccine will be administered during the late second or third trimester of pregnancy, within a permissible window (27 to 36 weeks gestation) that contains the ideal time period (28 to 32 weeks) for vaccination of pregnant women to protect their young infants. The choice of timing is based on an existing national recommendation in the US that was developed after taking into account the timing of maximal mother-to-fetus antibody transfer and the time needed for the pregnant woman to mount an immune response to vaccination. This period is also similar to the UK Department of Health recommendation for administering Tdap vaccine to pregnant women between 28 and 32 weeks gestation. This study is important because if we are able to demonstrate a beneficial effect of maternal Tdap vaccination on antibody responses in both mother and infant in a developing country setting, it would support incorporation of maternal prenatal Tdap immunization into routine immunization programs. Moreover, since pregnant women are already being vaccinated in developing countries as part of the effort to eliminate neonatal tetanus, Tdap could simply replace other tetanus toxoid containing preparations in these maternal vaccination programs.

Expected output Weblink to publication, influence immunization program recommendations

Project lead Saad B. Omer, MBBS PhD MPH

Type of activity Serologic analysis, impact on infant pertussis

Location Guatemala



Emory University, Universidad del Valle de Guatemala

Activity contact Saad B. Omer, MBBS PhD MPH


name Source of funding Thrasher Research Fund


Activity Identification Feasibility and best practice, regulatory support Activity title INFLUENZA VACCINES AND BIRTH OUTCOMES Activity objective Activity description

Develop a large database to be used for retrospective studies of potential adverse events following vaccination in pregnant women. The aim is to establish the data infrastructure and methodological framework within FDA's Sentinel system for studying adverse birth outcomes (e.g., congenital malformations) in this system.

Expected output Final Report and publication Project lead Alison Kawai Type of activity Vaccine Safety Location United States of America Activity start 2/25/2013 Activity end Implementing organization

FDA Sentinel


Michael Nguyen



Activity Identification Evidence generation,Feasibility and best practice,Regulatory support Activity title Feasibility of assessing safety and effectiveness of Tdap

vaccination in third-trimester pregnant women in Medicaid Activity objective The objective of this study is to evaluate the feasibility of using

Medicaid claims-based data to study vaccine safety and effectiveness in pregnant women and their infants. Using Tdap as a test case, we will examine the feasibility of identifying vaccine exposures during pregnancy and focus on the third trimester Tdap exposure and its relationship to birth outcomes and infant pertussis infections.


We propose to investigate the feasibility of using Medicaid claims-based data to study vaccine safety and effectiveness in pregnant women and their infants. Using tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) as a test case, we will focus on the evaluation of Tdap vaccine uptake in Medicaid pregnant women, the feasibility of linking mother-infant pairs and the feasibility of conducting cohort studies to study safety and effectiveness outcomes following maternal vaccine exposure during the third trimester of pregnancy.The overall goal of this study is to establish a methodological framework regarding design concerns for evaluating pregnancy outcomes and infant outcomes following maternal exposure to vaccination during pregnancy. We attemp to describe the characteristics of the Medicaid system and its claim-based data that are related to vaccine exposure during pregnancy. The infrastructure and methods development activity built through the results of this study will be used to determine the feasibility of pregnancy surveillance using the Medicaid claims-based data and to evaluate the methods required to conduct such surveillance.In this feasibility study, all results will be solely based on the electronic Medicaid claims-based data. Medical record review will not be conducted to verify the exposure, outcome, or any other variables or measures.

Expected output Publication(s) Project lead Yandong Qiang, MD, PhD Type of activity Methods developemnt and infrastructure buiilding for studying

vaccine safety and effectiveness in pregnant women and their infants in the Medicaid population

Location United States of America Activity start 10/1/2014 Activity end 9/30/2015 Implementing organization

FDA and CMS



Yandong Qiang

Source of funding FDA


Activity Identification Evidence generation, regulatory support, global collaboration

Activity title Pertussis vaccination during pregnancy

Activity objective -Determine the optimal time point for vaccination during pregnancy to protect both term and preterm born infants-Detect possible interference after maternal vaccination on the vaccine-induced infant immune response (accelular pertussis vaccine versus whole cell pertussis vaccine)-Monitor the compliance of the pertussis vaccination during pregnancy according to the recommendation in Belgium-Monitor the safety of pertussis vaccination during pregnancy -Determine the maternal immune response to pertussis immunization during pregnancy and the passive transfer of maternal pertussis antibody to the infant


Within the Center for the Evaluation of Vaccination, University of Antwerp, several research projects concerning maternal pertussis vaccination are ongoing. The ongoing research projects focusses on different aspects of pertussis immunization during pregnancy. 1) The effects of high loads of maternal antibodies aftervaccination during pregnancy are assessed in infants over time. Possible interference of maternal antibodies with the infant’s immune responses to its own vaccination are analyzed. Preliminary data showed a trend of interference of maternal antibodies on the infant pertussis immune response (called ‘blunting’) after administration of the third dose of a priming accelular pertussis vaccine (aP) schedule. The possible blunting effect disappeared with a fourth vaccine dose. However, so far interference results in children vaccinated with a whole cell pertussis vaccine (wP) after maternal vaccination during pregnancy have not been published. To perform this study, an international collaboration is set-up and a clinical trial is started in Bangkok, Thailand. Within this study, mothers are vaccinated with an aP vaccine during pregnancy. Children born from these mothers are vaccinated either with an aP or wP vaccine during infancy. Both the humoral immune responses (immunoglobulin G (IgG)) and the functionality of the maternal and vaccine-induced antibodies are analyzed. 2) Within a study performed in Belgium, both humoral (IgG) and cellular immune response are compared in term and preterm born infants after gestational pertussis vaccination. Since the transplacental transport mechanisms is immature before 32 weeks of pregnancy, preterm born infants receive less transplacentally transferred maternal antibodies. However, the amount of immunoglobulin A (IgA) in breast milk might compensate if the transplacentally acquired maternal antibodies are not sufficient in preterm born infants. Therefore, breast milk samples are analyzed in a standard way to determine the amount of IgA and IgG in breast milk. With this study, we want to determine the optimal time point for vaccination during pregnancy to protect both term and preterm born infants. 3) In Belgium, maternal pertussis vaccination is recommended for every pregnant women during each pregnancy between 24 and 32 weeks of gestation. To monitor the compliance of the new recommendation, surveys are conducted within the target


population (women who recently gave birth, health care workers) among Flanders. 4) A pilot study on pertussis immunization during pregnancy is already performed in parallel in Belgium and Vietnam. Within this study, a study group of pertussis immunized women (Boostrix® or Adacel®) during pregnancy was compared to a control group. All children of these women were immunized with an acellular pertussis vaccine during infancy. Blood samples were taken at several time point throughout the study to monitor the humoral immune response. At the moment, this pilot study is nearing its end and output is expected in the near future.

Expected output International peer reviewed publications, presentations on international congresses...

Project lead Prof. Dr. Elke Leuridan, Prof. Dr. Pierre Van Damme

Type of activity Vaccine trials in pregnant women, surveys in pregnant women to assess the knowledge for vaccine policies targeting pregnant women.

Location Belgium



University of Antwerp


Prof. Dr. Elke Leuridan, Drs. Kirsten Maertens

Source of funding Research Foundation Flanders + Thrasher Research Fund + University of Antwerp internal funding


Activity Identification Evidence generation, policy development, global collaboration

Activity title Surveillance phace: Baseline surveillance to identify the burden or Pertussis in early infancy in Pakistan; Trial phase: Efficacy and Immunogenicity of Tdap immunization of pregnant women for preventing Pertussis in early infancy in Pakistan

Activity objective SURVEILLANCE PHASE:Objective 1:To estimate the incidence of pertussis in the first 18 weeks of lifeObjective 2:To evaluate a modified version of the Preziosi scale of pertussis severity to classify pertussis severity (i.e. mild, moderate, severe disease)TRIAL PHASE:Objective 1:To evaluate field efficacy and safety of maternal vaccination with Tdap administered during a permissible window within the third trimester of pregnancy (27 to 36 weeks gestation) to protect young infantsObjective 2:To determine antibody responses to Tdap in pregnant women and their infants up to 18 weeks of age and antibody responses to DTwP in infantsa) To assess antibody transfer from mother to infant after Tdap vaccination during pregnancyb) To assess differential attenuation of the infant’s immune response to DTwP associated with maternal Tdap vaccination or non-vaccination during pregnancy


The project is a two-phase study. Phase one will be a Surveillance Phase to estimate the incidence of pertussis within the first 18 weeks of life, while evaluating disease severity. Phase two will be the Trial Phase, and will include a phase III randomized, double-blind, controlled, field implementation trial to evaluate the efficacy of maternal Tdap immunization during the third trimester of pregnancy, within a permissible window (27 to 36 weeks gestation) containing the ideal vaccination period (28 to 32 weeks) for vaccination of pregnant women to protect young infants. The choice of timing is based on an existing national recommendation in the US that was developed after taking into account the timing of maximal mother-to-fetus antibody transfer and the time needed for the pregnant woman to mount an immune response to vaccination. This period is also similar to the UK Department of Health recommendation for administering Tdap vaccine to pregnant women between 28 and 32 weeks gestation.5 This study is important because, should Tdap be shown to prevent infant pertussis in a developing country setting, it would be possible to incorporate maternal prenatal Tdap immunization into routine immunization programs, since pregnant women are already being vaccinated in developing countries as part of the effort to eliminate neonatal tetanus. Thus, Tdap can simply replace other TT containing preparations in these maternal vaccination programs.


Project lead Saad B. Omer, MBBS PhD MPH


Type of activity Serologic analysis, impact on infant pertussis Location Pakistan Activity start 7/1/2014 Activity end 4/30/2018 Implementing organization

Emory University, Aga Khan University


Saad B. Omer, MBBS PhD MPH



Activity Identification Evidence generation, policy development, feasibility and best practice, regulatory support, ethics and liability issues, global collaboration

Activity title Maternal Immunization Portfolio

Activity objective to develop an evidence-based maternal immunization platform that will significantly reduce mortality due to infectious causes in the first six months of life


The maternal immunization portfolio is focused on the following activities for five pathogens, including RSV, influenza, group B strep, pertussis, and tetanus: 1) Evidence Generation: Ensure sufficient cost effectiveness, health impact, and burden data to support internal and external (national policy and funding) decisions2) Safety & Efficacy: Demonstrate efficacy of vaccines in protecting infants via maternal immunization 3) Vaccine Development: Develop vaccines that address via maternal immunization the significant infectious causes of neonatal and young infant mortality4) Cross-cutting Implementation: Establish global capability to implement, monitor, and measure maternal immunization programs5) Immunization Policy: Enable adoption of global and national policies for maternal immunization

Expected output

Project lead Niteen Wairagkar serves as the Initiative Lead for RSV and Influenza, including all maternal immunization activities for these pathogens. Ajoke Sobanjo-ter Meulen is the Initiative Lead for Maternal Immunization, including Group B Strep, Pertussis, Tetanu

Type of activity




The Bill & Melinda Gates Foundation is funding a wide variety of grantees to implement maternal immunization activities.


Ajoke Sobanjo-ter Meulen, Maternal Immunization Lead Niteen Wairagkar, RSV & Influenza Lead



Activity Identification Regulatory support, training and tools, global collaboration

Activity title GAIA - Global Alignment of Immunization safety Assessment in pregnancy

Activity objective GAIA aims to provide standards and tools to establish a globally shared understanding of outcomes and approaches to monitoring them with specific focus on LMIC needs and requirements.


GAIA is a 2 year project, building on the WHO initiative to develop case definitions for key events related to immunisation in pregnancy. GAIA is coordinated by the Brighton Collaboration Foundation with core funding by the Bill and Melinda Gates Foundation. Outputs will be developed by the consortium partners including WHO and will be developed in close interaction with a global network of stakeholders and experts to ensure global applicability and usefulness of the standards developed.

Expected output Case definitions of key obstetric and neonatal outcomes, Shared terminology and code mapping, Tools for harmonised data collection, Evaluation and implementation

Project lead Jan Bonhoeffer

Type of activity standards, harmonisation, method and tool development, capacity building




Brighton Collaboration Foundation


Jorgen Bauwens



Activity Identification Evidence generation, policy development, feasibility and best practice, training and tools

Activity title Protecting pregnant women From infectious diseases: a cluster randomized evaluation of the comprehensive “P3” intervention packaged within obstetric practices in Georgia

Activity objective Primary Outcome Measures:Receipt of influenza vaccine during pregnancy [ Time Frame: Participants will be followed for the remaining duration of their pregnancy, which will range from approximately 2 weeks to 7 months depending upon their gestation at enrollment. ]Our primary outcome is receipt of a 2012 - 2013 seasonal influenza vaccine during a participant's current pregnancy, before she delivers her child(ren).Secondary Outcome Measures:Receipt of Tdap vaccine during pregnancy [ Time Frame: Participants will be followed for the remaining duration of their pregnancy, which will range from approximately 2 weeks to 7 months depending upon their gestation at enrollment. ] A secondary outcome is receipt of a Tdap vaccine during a participant's current pregnancy, before she delivers her child(ren).Other Outcome Measures: Changes in maternal knowledge, attitudes and beliefs regarding maternal and infant vaccination [ Time Frame: Participants will be followed for the remaining duration of their pregnancy, which will range from approximately 2 weeks to 7 months depending upon their gestation at enrollment. ] This secondary outcome will be assessed through two surveys: one survey administered at baseline upon enrollment, and another survey administered 2 - 3 months post-partum.


The primary research aim of this project was to test the effectiveness of a comprehensive, evidence-based vaccine promotion package implemented in the obstetric setting on increasing the likelihood that a pregnant woman in Georgia will receive an influenza vaccine and/or Tdap vaccine before delivery. A secondary research aim assessed whether the comprehensive package improves maternal knowledge, attitudes, and beliefs regarding maternal and infant vaccination. The intervention package included evidence-based components aimed at the practice-level, provider-level, and patient level and will be tested through a cluster-randomized trial design. The primary outcome measure was influenza vaccine receipt during pregnancy. The secondary outcomes included 1) receipt of pertussis (Tdap) vaccination during pregnancy, and 2) changes in maternal knowledge, attitudes and beliefs regarding maternal and infant vaccination. The primary hypothesis was that implementation of a comprehensive vaccine promotion package in the obstetric setting will increase the likelihood that a pregnant woman receives an influenza and/or pertussis vaccination.



Project lead Saad B. Omer, MBBS PhD MPH Type of activity Knowledge gain, uptake of maternal vaccinations, attitudes

surrounding maternal vaccinations Location United States of America Activity start 12/1/2012 Activity end 2/1/2014 Implementing organization

Emory University



Source of funding Centers for Disease Control and Prevention


Activity Identification Evidence generation, global collaboration Activity title Prospective community-based study of RSV risk factors in

Nepalese children Activity objective Young investigator training grant to become an independent

researcher. Activity description

Identify the host and virologic factors that lead to respiratory syncytial virus (RSV) disease in Nepalese children

Expected output Publication Project lead Helen Ying-Hui Chu Type of activity analysis of diesease trends Location Nepal Activity start 6/24/2013 Activity end 5/31/2018 Implementing organization



Sonnie Kim



Activity Identification Evidence generation, policy development, feasibility and best practice, training and tools Activity title Innovative strategies to combat vaccine refusal in minority

Populations Activity objective Improve the uptake of influenza and pertussis vaccines in

pregnancy, and influence maternal vaccine knowledge, attitudes and beliefs regarding maternal and infant vaccination.


While the prenatal period is an opportune time for health education, often referred to as the “teachable moment”, vaccine education during the prenatal period is under-utilized and has not been rigorously evaluated for efficacy. This project tested two vaccine education strategies during the prenatal period. The education strategies were based on the elaboration likelihood model (ELM). This model is based on experimental psychology and has been previously used to increase breast cancer screening rates. These education strategies were delivered through routine prenatal care visits to African-American women in Atlanta. Outcome measures included uptake of influenza and pertussis vaccines in pregnancy and maternal vaccine knowledge, attitudes, and beliefs regarding maternal and infant vaccination.

Expected output Weblink to publication Project lead Saad B. Omer, MBBS PhD MPH Type of activity Knowledge gain, uptake of maternal vaccinations, attitudes

surrounding maternal vaccinations Location United States of America Activity start 3/1/2012 Activity end 12/31/2012 Implementing organization

Emory University



Source of funding Kaiser Foundation Research


Activity Identification Evidence generation, training and tools Activity title Vaccine development for Falciparum malaria in pregnant

women and their offspring Activity objective Training of clinical researcher Activity description

The objective of this proposal is to identify conserved Plasmodium falciparum antigens that are uniquely recognized by IgG antibodies in venous blood obtained at delivery from mothers whose infants survived their first year of life with mild or no clinical malaria

Expected output Publication Project lead Ian C. Michelow Type of activity Analysis of disease trends Location All countries Activity start 7/1/2013 Activity end 6/30/2018 Implementing organization

Rhone Island Hospital


Malla R. Rao



Activity Identification Evidence generation, policy development, global collaboration Activity title Ongoing studies in maternal immunisation MRC Unit, The

Gmabia Activity objective to ascertain if vaccination against pneumococcus in pregnancy

protects the newborn from acquisition of pneumo carriage Activity description

RCT

Expected output Publication Project lead Dr Ed Clarke Type of activity RCT Location Gambia Activity start 3/1/2015 Activity end 3/1/2015 Implementing organization

MRC Unit, The Gambia


Professor Beate Kampmann, Director of Vaccinology research

Source of funding DFID/MRC/WT Global Trials scheme


Activity Identification Evidence generation, policy development, feasibility and best practice, training and tools Activity title A comprehensive pre-natal intervention to increase vaccine

coverage Activity objective Specific Aim 1:Refine our P3 intervention based upon what we

learned in our pilot study and additional formative, qualitative research, to develop the P3+ intervention package.Specific Aim 2:Evaluate the P3+ intervention


Vaccination of pregnant women can impart health benefits on the unborn and infant child, and increased acceptance of maternal vaccination may lead to increase in acceptability of childhood vaccination. However, maternal vaccination rates are low, and new comprehensive, evidence-based interventions are needed to increase vaccination uptake among pregnant women and their children. We developed and pilot tested an innovative, evidence based, and comprehensive intervention at the Practice, Provider, and Patient (P3) levels. For the current project, we will update and refine the P3 intervention to develop the second generation, P3+, intervention. This project will also rigorously evaluate the intervention. The P3+ intervention will contain the following components:1) Practice-level intervention will include: a. Identification and utilization of a vaccine champion in the medical office, b. Use of informational posters about immunization in practice waiting rooms, and c. Use of standing orders for maternal immunization.2) Provider-level intervention will include a. An online CME module covering vaccine preventable diseases, maternal and childhood vaccines, and common vaccine questions and misconceptions encountered in the clinical setting, b. An online module for strategies to incorporate vaccination into standard office workflow and information on how to order, store, and bill for immunizations delivered, and c. Provision of written vaccine information, including standardized talking points for maternal and infant vaccines. 3) Patient-level intervention will include an interactive tablet computer (iPad) based application (‘app’) that will deliver tailored educational materials, based on responses given to the initial baseline questionnaire.

Expected output Weblink to publication Project lead Saad B. Omer, MBBS PhD MPH; Daniel Salmon, Phd MPH Type of activity Knowledge gain, uptake of maternal vaccinations, attitudes

surrounding maternal vaccinations Location United States of America Activity start 11/1/2014 Activity end 10/31/2019



Emory University, Johns Hopkins University



Source of funding National Institutes of Health


Activity Identification Policy development, training and tools, ethics and liability issues, global collaboration Activity title Early post-partum influenza vaccination of women aiming

to protect them and their young infants Activity objective To study the feasibility and effectiveness of the abovementioned

intervention in reducing influenza-like illness, morbidity, antibiotic use and hospitalizations im young infants during the influenza season.


Vaccination of women early post-partum, before discharge from the hospital.

Expected output http://cid.oxfordjournals.org/content/57/11/1520.long Project lead Helena Maltezou Type of activity vaccine effectiveness Location Greece Activity start 10/1/2012 Activity end 5/1/2013 Implementing organization

Hellenic Center for Disease Control and Prevention, University of Athens, Athens, Greece


Helena Maltezou

Source of funding Caccine company


Activity Identification Policy development, feasibility and best practice, evidence generation Activity title Influenza vaccine utilization in pregnant women Activity objective Monitor vaccine uses in pregnant women Activity description

Providers report daily doses of influenza vaccines administered to pregnant women through the Influenza Vaccine Information System (IVIS)

Expected output Weekly reports during nationwide mass immunization campaign Project lead Wan-Ting Huang MD Type of activity Vaccine coverage Location Taiwan Activity start 1/10/2014 Activity end Implementing organization

Taiwan Centers for Disease Control


Wan-Ting Huang MD

Source of funding Taiwan Centers for Disease Control


Activity Identification Evidence generation Activity title Simple interventions to improve rotarvirus vaccine

effectoveness (SIRVE) Activity objective Address the problem of low rotavirus vaccine performance in low

and middle income countries (LMICs). Activity description

This study brings together a team of investigators from diverse disciplines to address the problem.

Expected output Publications Project lead Sylvia I. Becker-Dreps Type of activity vaccine effectivness Location All countries Activity start 8/1/2014 Activity end 7/31/2015 Implementing organization

University of Noth Carolina Chapel Hill


Sylvia I. Becker-Dreps

Source of funding NIAID


Activity Identification Evidence generation

Activity title Infant respiratory outcomes associated with prenatal exposure to maternal H1N1 influenza vaccination

Activity objective To evaluate the effect of maternal H1N1 vaccination during pregnancy on rates of infant respiratory illness


We used a population-based maternal-child registry to identify a one-year live birth cohort in Ontario, Canada in 2009–2010. Infant records containing data on maternal H1N1 vaccination during pregnancy were linked with health care databases to measure rates of influenza and other respiratory infections diagnosed during ambulatory physician visits, hospitalizations and emergency department (ED) visits within the first year following birth. We estimated incidence rate ratios (IRR) and 95% confidence intervals (CI) using Poisson regression, comparing event rates among infants born to H1N1-vaccinated women with unexposed infants, adjusted for confounding using high-dimensional propensity scores.

Expected output Peer-reviewed scientific publication

Project lead Deshayne Fell

Type of activity Analysis of rates of influenza and pneumonia among infants exposed to monovalent H1N1 vaccine in utero, relative to unexposed infants

Location Canada



Better Outcomes Registry & Network (BORN) Ontario and the Institute for Clinical Evaluative Sciences (ICES)


Deshayne Fell

Source of funding Canadian Institutes for Health Research


Activity Identification Evidence generation Activity title Overcoming maternal antibody-mediated

immunosuppresion Activity objective Understanding how to activate the infant immune system in the

presence of maternal antibodies Activity description

Characterize the infant immune responses induced by soluble antigens in the presence of maternal antibodies. probe the extent of this protective immunity using H1N1, H3N2 and H5N1 influenza virus challenge models. determine the extent to which maternal antibody mediated suppression can be overcome in non-human primate, rhesus macaque infants.

Expected output Publication Project lead Joshy Jacob Type of activity vaccine effectiveness Location All countries Activity start 8/21/2012 Activity end 7/31/2017 Implementing organization

Emory University


Christopher E. Beisel




Activity title Follow-up and active surveillance of trivalent influenza vaccine in mums (FASTMum) and the maternal influenza vaccination in Western Australia (MIV-West) cohort

Activity objective 1) To monitor the safety of influenza vaccines administeredduring pregnancy in Western Australia.2) To evaluate the effectiveness of maternal influenza immunisation in preventing hospitalisations and infections in mothers and infants.3) To assess the health of infants born to mothers immunised against influenza during pregnancy to infants born to unimmunised mothers.


Initiated in 2012, the FASTMum program is an active vaccine safety surveillance program which routinely follows up pregnant women who received trivalent influenza vaccine in Western Australia. The program uses short message services (SMSs) to measure adverse events following immunisation seven days post-vaccination. Women who report experiencing a reaction are administered a survey to collect details related to the adverse event. Data collection coincides with vaccination, which begins 15 March each year. The MIV-West cohort is a longitudinal cohort study in Western Australia established in 2012 using linkages of state-based datasets, including midwifery and birth records, vaccination records, disease notifications, and hospital records. The cohort was established with the intention of evaluating the effectiveness of maternal influenza immunisation in preventing infection in infants and mothers. The cohort currently includes 60,000 births between 2012 and 2013 in Western Australia.

Expected output Communications with antenatal care providers and the public regarding the safety and effectiveness of immunisation during pregnancy; peer-review publications

Project lead Dr Paul Effler, Medical Coordinator, Communicable Disease Control Directorate, Western Australia Department of Health

Type of activity Monitoring of vaccine safety information and vaccine effectiveness

Location Australia



Communicable Disease Control Directorate, Western Australia Department of Health


Annette Regan, PhD Candidate, Communicable Disease Control Directorate, Western Australia Department of Health

Source of funding Communicable Disease Control Directorate, Western Australia


Department of Health


Activity Identification Evidence generation Activity title Maternal stress, obesity, and influenza virus vaccine

immunogenicity in pregnancy Activity objective Activity description

This study will examine effects of everyday life stress and obesity on immune responses to influenza virus vaccine (the flu shot) during pregnancy. Following vaccination, antibody levels against influenza (the flu) increase. Higher antibody levels indicate better immune protection from influenza. In addition to providing protection from the flu for yourself, being vaccinated during pregnancy may protect your baby from the flu during the first six months of life during which time infants cannot be vaccinated. Our goal is to determine whether greater life stress and obesity reduce 1) antibody responses to the flu shot in women and 2) antibody levels in the newborn at the time of delivery.

Expected output publications Project lead Lisa M. Christian, PhD Type of activity behavioral modifiers of influenza vaccine immunogenicity Location United States of America Activity start 1/8/2013 Activity end 1/5/2018 Implementing organization

The Ohio State University Wexner Medical Center


Lisa M. Christian

Source of funding NIH



Activity title Efficiency of RSV-specific maternal antibody transfer in developing country populations

Activity objective Understanding efficiency of RSV-specific maternal antibody transfer in a Papua New Guinea population


Leveraging maternal/cord blood pairs collected as part of a malaria study to assess efficiency of RSV-specific maternal antibody transfer in a Papua New Guinea population.

Expected output Journal publication

Project lead Ruth Karron

Type of activity Feasibility of using a maternal immunization strategy for RSV

Location Papua New Guinea



Johns Hopkins School of Public Health


Ruth Karron

Source of funding PATH


Activity Identification Evidence generation Activity title Global survey of surveillance systems for AEFI in pregnant

women and their infants Activity objective To set baseline for surveillance systems- active and passive for

AEFI in pregnant women and thier infants Activity description

Survey of 143 countries NRAs etc to ask if any AEFI surveillance system in place for pregnant women and their infants . Earlier systematic review had found little published in this area and no reports of specific systems ongoing. Several of the passive AEFI rpeorting systems in high income countries do not specifically ask in pregnant on form

Expected output Baseline level from which can see if improves with interventions Project lead Noni MacDonald , Karina Top Type of activity survey Location All countries Activity start 11/15/2014 Activity end 6/1/2015 Implementing organization

Canadian centre for Vaccinology with WHO


Noni MacDonald , Karina Top



Activity Identification Evidence generation Activity title Activity objective Activity description

Clinical study of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) safety in pregnant women

Expected output publication Project lead Type of activity vaccine safety Location United States of America Activity start Activity end Implementing organization

CDC/Clinical Immunization Safety Assessment (CISA) Project


Karen Broder

Source of funding



Feasibility of monitoring nnfluenza vaccine safety in pregnant women using text messaging


CDC


Karen Broder

Source of funding


Activity Identification Evidence generation Activity title Causes of Rotavirus vaccine failure in Zambian children Activity objective vaccines can be less immunogenic and efficacious in developing

world settings as compared with industrialized countries. Reasons behind this phenomenon are not well understood


study will recruit a prospective cohort of 420 mother-infant pairs. Participants will be enrolled at the time of vaccination and followed for up to four years. Baseline immunological status will be ascertained and seroconversion rates determined a month after full immunization. Incident rotavirus gastroenteritis will be monitored in the vaccinated infants whenever episodes of diarrhea occur; through this surveillance, the sero-strains of rotaviruses causing disease will be tracked over the four year period.

Expected output publication Project lead CHILENGI, ROMA Type of activity vaccine effectiveness Location Zambia Activity start 8/1/2012 Activity end 7/31/2017 Implementing organization

CENTRE FOR INFECTIOUS DISEASE RESEARCH, Zambia


Rodolfo M. Alarcon




Activity title Assessment of the effect of placental malaria and hypergammaglobulinemia on transplacental transport of respiratory syncytial virus (RSV) antibodies in Papua New Guinea

Activity objective Determine the impact of placental malaria and hypergammaglobulinemia on transplacental transfer of RSV-specific antibodies between Papua New Guinean mother-infant pairs from two temporally disparate cohorts with very different rates of placental malaria


Measure RSV neutralizing antibodies in maternal and cord sera in two study cohorts; analyze effect of placental malaria, maternal hypergammaglobulinemia and other demographic variables on transfer.

Expected output publication (ms to be submitted March 2015)

Project lead Ruth Karron

Type of activity analysis of some potential biologic barriers to transplacental Ab transfer

Location Papua New Guinea



Johns Hopkins Bloomberg School of Public Health


Ruth Karron

Source of funding PATH


Activity Identification Evidence generation Activity title Host and parasite factors that influence susceptibility t

malaria infection and disease during pregnnacy and early shildhood in Quelessebougou and Bamako, Mali

Activity objective Assess the relationship between malaria exposure during

prengnancy and maternal and fetal oucomes. Activity description

Up to 2000 pregnant women and their infnats will be enrolled and followed until 5 years of age with periodic blood sampling.

Expected output Publication Project lead Michal Fried, Patrick Duffy Type of activity Analysis of disease trends Location Mali Activity start 6/1/2010 Activity end Implementing organization

NIH Clinical Cener


Michal Fried



Activity Identification Evidence generation Activity title Department of Defense (DoD) Birth and Infant Health

Registry Activity objective The primary objective of the DoD Birth and Infant Health Registry

is to increase the understanding of the reproductive health effects of military service by providing systematic surveillance of DoD beneficiary births and scientifically rigorous research of infant health outcomes


The US Department of Defense (DoD) is challenged with monitoring and protecting the health of its service members and their families. The growing number of women on active duty and the diverse occupational exposures associated with military service make reproductive health issues a special concern for the DoD. The DoD Birth and Infant Health Registry has established direct access to large databases for thorough capture of all birth and health outcomes up to the first birthday in infants born to military families. Scientific protocols are developed to evaluate epidemiologic associations between these outcomes and specific exposures of concern, including military occupations and military-unique exposures of concern such as vaccination during pregnancy. The DoD Birth and Infant Health Registry responds to the needs of young military families in addressing their reproductive health concerns with strong science and surveillance. These projects focus research on appropriate health risks and contribute to the understanding and progress in the prevention of birth defects and other infant health challenges

Expected output Annual Reports, Peer-Reviewed Manuscripts, Responses to

Inquiries Project lead Dennis Faix, MD, MPH (CDR, MC, USN); Ava Maris S. Conlin, DO,

MPH Type of activity Surveillance of birth defects and other adverse infant health

outcomes (preterm birth, growth problems in utero and in infancy, male:female sex ratio). Analyses of epidemiologic associations between infant health outcomes and exposures of interest including vaccination during pregnancy.

Location United States of America Activity start 17/11/98 Activity end Implementing organization

Naval Health Research Center, San Diego, CA, USA

Activity contact Ava Marie S. Conlin, DO, MPH


name Source of funding United States Department of Defense


Activity Identification Evidence generation Activity title Clinical trials of vaccines for respiratory Syncytial virus

and related viruses Activity objective Developing live attenuated vaccines against RSV, HPIV3, HMPV,

HPIV1, and HPIV2 (in decreasing order of importance) Activity description

Vaccines are developed and produced from cloned cDNAs using reverse genetic systems of our making and employ defined attenuating mutations of our making. We develop candidates in pre-clinical studies and prepare vaccine seeds. Vaccine manufacture is performed under contact under our supervision, and clinical evaluation is performed by contract or collaboration under our supervision. Vaccines are evaluated clinically beginning in adults (who are seropositive for these common viruses), and moving successively to seropositive older children (typically 12-59 months of age) followed by seronegative younger children and infants (typically 6 -24 months of age for RSV, 6-59 months of age for the others). For RSV and HPIV3, viruses may be evaluated further in virus-naive young infants 1-3 months of age. Adult studies are open-label, whereas pediatric studies are double-blind placebo-controlled with a 2:1 ratio of vaccine to placebo recipients. For all RSV studies, subjects are followed during the subsequent RSV season (Nov 01 March 31).

Expected output Publication Project lead Peter Leon Collins Type of activity Vaccine effectiveness Location United States of America Activity start Activity end Implementing organization

NIH


Source of funding NIH


Activity Identification Evidence generation Activity title PREGNANCY MALARIA: PATHOGENESIS AND IMMUNITY Activity objective Develop pregnancy malaria vaccines that will protect women

through production of anti-adhesion antibodies Activity description

CSA binding in placenta can be inhibited by treating parasites with sera from multigravida women of malaria endemic area or animals immunized with antigens critical for parasite adhesion.

Expected output Publication Project lead Patrick Duffy Type of activity Analysis of disease trends Location All countries Activity start Activity end Implementing organization

National Institute of Allergy and Infectious Diseases (NIAID)


Source of funding NIAID/NIH



Activity title Maternal immunization to prevent neonatal deaths from sepsis and meningitis in GAVI-eligible, sub-Saharan African countries: Cost-effectiveness of group B streptococcal vaccine

Activity objective We propose to analyze the value of maternal vaccination against group B streptococcus in helping low-income sub-Saharan African countries prevent neonatal deaths, in order to achieve Millennium Development Goal 4.


Context. Group B streptococcus (GBS) is a leading neonatal sepsis pathogen globally, a major contributor to neonatal deaths in the world’s poorest countries, and has a particularly high burden of disease in Africa, where half the GAVI-eligible countries are located. In wealthy countries, intrapartum antibiotic prophylaxis (IAP), based on culturing pregnant women for GBS weeks before delivery, has greatly reduced neonatal GBS disease, but the strategy is not feasible in low-income countries. Risk factor-based IAP (RFB-IAP) during delivery, for women with risk factors such as intrapartum fever, is less complex and costly, but still difficult to implement in resource-poor settings. A maternal vaccine to prevent GBS disease in newborns is in Phase II trials in South Africa; planning has begun for Phase III licensure trials. Maternal immunization programs, already offering tetanus toxoid vaccines, offer a platform with untapped potential to improve health on which to build a GBS immunization effort, although at additional cost. The cost-effectiveness analysis we propose is the first, to our knowledge, to consider maternal immunization as a means of reducing neonatal mortality in low-income countries.Project goal. To speed funders’ decisions about maternal GBS vaccination, once Phase III trials establish efficacy, we will evaluate its potential cost and public health impacts (cases prevented, lives saved, disability-adjusted life years [DALYs] averted) in the low-income sub-Saharan region. Building on an established projection model that meets the high standards needed for evidence-based policy decisions, our evaluation will identify key drivers and decision thresholds for factors (such as disease incidence) critical to the success of vaccination. It will provide the information needed to decide whether, and under what conditions, maternal GBS vaccination programs would be a good public health investment in this high burden region. Working with the Centers for Disease Control and Prevention (CDC), South African colleagues, and other GBS disease experts, we have already evaluated maternal GBS vaccination in South Africa, a middle-income country. Using a projection model to compare vaccination, RFB-IAP, and vaccination plus RFB-IAP, we found that a vaccine that is 50%-90% effective against covered serotypes would prevent 29%-53% of infant GBS deaths, and do so very cost-effectively. We will use that model as a foundation and refit it as appropriate for low-income sub-Saharan Africa. Objectives and milestones:• Fitting the model with data that reflect conditions and policy options in low-income sub-Saharan


countries is a crucial step for evidence-based policy. The process requires a network of regional and international experts to help locate published and unpublished data, together with up-to-date statistical methods, including meta-analysis, to evaluate, analyze, and synthesize the data.• At the end of the first year we will deliver a preliminary evaluation of the public health impact (cases, deaths, and DALYs averted), costs, and cost-effectiveness of maternal GBS vaccination to the Gates Foundation, including identification of key drivers and decision thresholds.• We will then continue building the model to permit probabilistic sensitivity analysis; we will conduct extensive sensitivity analyses, including value of information analyses (VOI), to complete identification of key drivers, decision thresholds, and insights into where research investments provide good value. • The final report will evaluate the cost-effectiveness of maternal GBS vaccination in low-income sub-Saharan Africa to show where and how investment in the vaccine might be a good public health investment. Based on value of information analyses, the report will recommend new research on such possible key drivers as maternal GBS colonization, disease incidence, and serotype prevalence.

Expected output Technical reports, publications

Project lead Anushua Sinha

Type of activity health economic analysis

Location Benin,Burkina Faso,Burundi,Cameroon,Cape Verde,Central African Republic,Chad,Congo,Cote d'Ivoire,Democratic Republic of the Congo,Equatorial Guinea,Ethiopia,Gabon,Gambia,Ghana,Guinea,Guinea-Bissau,Lesotho,Liberia,Madagascar,Malawi,Mauritania,Mauritius,Mozambique,Namibia,Niger,Nigeria,Senegal,Sierra Leone,Sudan,Uganda,United Republic of Tanzania,Zambia,Zimbabwe



Rutgers University


Anushua Sinha




Activity title Southern Africa mother infant pertussus study (Phase I) - SAMIPS1

Activity objective To determine the incidence of Severe and Non-Severe pertussis among Zambian infants from birth through 14 weeks of age


Prospective birth cohort including 2000 mother infant pairs, sampled every 2-3 weeks for syndromic def of possible pertussis; NP swabs obtained irrespective of symptoms according to this schedule; additional NP swabs obtained at respiratory sick visits. NP swabs from symptomatic mother/infant pairs will be tested using PCR for B. pertussis. Results from study will enhance our understanding of epidemiology of early infant pertussis; shed light on the role of maternal HIV status on infant pertussis; better define the symptomatology of infant pertussis; and provide foundation for sample size calculations for planned RCTs of maternal Tdap. This study is being coordinated with similar epidemiologic studies in Johannesburg and Karachi Pakistan. All three sites will also be part of the consortium of sites in the planned RCTs.

Expected output Weblink to publications; meeting reports also possible

Project lead Christopher Gill

Type of activity Analysis of disease incidence

Location Zambia



Boston University School of Public Health


christopher gill



Activity Identification Evidence generation Activity title PneumoTone Activity objective To determine the incidence and etiology of all-age pneumonia in

the Tone District of Northern Togo and to measure the impact of PCV on pneumonia incidence


Surveillance of pneumonia with a variety of diagnostic modalities, including blood culture, nasopharyngeal carriage, nasal wash, PCR. PCV will be introduced into the infant EPI program and changes in disease incidence monitored. Pregnant women are not excluded so we will have data on pneumonia burden among pregnant women and indirect protection provided by PCV.

Expected output Meeting report, publication Project lead Jennifer Moisi Type of activity Surveillance, etiology, vaccine effectiveness Location Togo Activity start 1/1/2011 Activity end Implementing organization

AMP


Jennifer Moisi

Source of funding BMGF, Pfizer, CDC Foundation



Chorioamnionitis reports after vaccination in VAERS

Expected output publications Project lead Type of activity vaccine safety Location United States of America Activity start Activity end Implementing organization



Maria Cano

Source of funding


Activity Identification Evidence generation Activity title Pregnancy as a risk factor for severe outcomes from

influenza: a systematic review and meta-analysis Activity objective To quantify the effect of pregnancy on severe influenza-

associated disease and to summarize the evidence for pregnancy as a risk for severe influenza disease.


Systematic review and meta-analysis of observational studies including cohort, case-control, cross-sectional and ecological studies that reported on pregnancy as a risk factor for severe outcomes from influenza virus infection

Expected output Report and publication Project lead Mark Loeb Type of activity Systematic review and meta-analysis Location Canada Activity start 1/1/2014 Activity end 1/1/2015 Implementing organization

McMaster University


Mark Loeb



Activity Identification Evidence generation Activity title Influence of timing of maternal immunization on neonatal

immunity against pertussis Activity objective To assess if the GMT of anti-pertussis toxin (PT) antibodies in the

cord blood of neonates from mothers immunized against pertussis during the 2nd trimester (13 to 25 weeks of gestation) is not inferior to those from mothers immunized during the 3rd trimester (as of 26 weeks).


Single center, cross-sectional non-inferiority study assessing anti-pertussis antibodies in cord-blood of immunized mothers.

Expected output publication Project lead Claire-Anne Siegrist Type of activity Surrogate for maternal immunization effectiveness study Location Switzerland Activity start 4/1/2014 Activity end Implementing organization

University Hospitals of Geneva, Switzerland


Prof. Claire-Anne Siegrist

Source of funding University Hospitals of Geneva, Switzerland



Activity title Clinical trial

Activity objective To assess the safety and immunogenicity of Tdap during pregnancy


RCT of Tdap vs Td in the 3rd trimester of pregnancy; assessing AEFI in the women and the immune response to routine immunization in the newborns. Follow up of infants through their booster in the second year of life.

Expected output presentations/publications

Project lead Scott Halperin, MD

Type of activity vaccine safety and immunogenicityc

Location Canada

Activity start Activity end 5/31/2015


Canadian Center for Vaccinology


Scott Halperin

Source of funding sanofi pasteur



Immune and hormone response to influenza


CDC/ Clinical Immunization Safety Assessment (CISA) Project


Karen Broder

Source of funding


Activity Identification Evidence generation Activity title WHO taskforce to evaluate influenza data to inform vaccine

impact and economic modelling Activity objective 1. To determine key parameters needed for influenza vaccine

impact and health economic modelling studies, with a focus on immunization in low-resource settings and pregnant women2. To determine evidence-based estimates for these key parameters3. To evaluate the quality of existing data informing these estimates4. To recommend future research to address existing data gaps


As part of the WHO maternal influenza immunization agenda, the WHO Initiative for Vaccine Research (IVR) is convening a Taskforce to advise in the review of key variables for influenza vaccine impact and health economic modelling studies. The Taskforce is reviewing influenza disease incidence data relevant to pregnant women, newborn children, and the fetus, as well as vaccine performance to prevent influenza disease in pregnancy and during the first 6 months of life. The Taskforce will inform efforts by IVR to promote evidence-based implementation research for influenza vaccine programs. Work undertaking is part of the WHO Framework of Vaccine-preventable disease burden and impact assessment as endorsed by the WHO Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC).

Expected output Preliminary results will be presented to WHO in March 2015. Final

reports to WHO are expected in third quarter 2015. Results will be presented to Immunization and Vaccines Related Implementation Research Advisory Committee, tentatively in 3rd quarter 2015.

Project lead Taskforce chairperson is Brad Gessner. Taskforce supported by

WHO IVR. Type of activity Synthesis of disease incidence data and vaccine effectiveness

data with review by expert group of epidemiologists. Location All countries Activity start 11/1/2014 Activity end 6/1/2014 Implementing organization

WHO IVR


Justin Ortiz




Tdap/HPV/Influenza vaccine safety in pregnancyTrivalent influenza vaccine and spontaneous abortion, 2010-2012Influenza vaccination during pregnancy (coverage 2001-2012)Safety of Tdap vaccination in pregnant women following prior tetanus containing vaccinesTdap immunization in pregnant women and co-administration with influenza vaccineSafety of hepatitis A and B vaccines during pregnancy

Expected output publications Project lead Type of activity Location United States of America Activity start Activity end Implementing organization

CDC/Vaccine Safety Datalink (VSD) Project


Michael McNeil

Source of funding



Safety of seasonal influenza vaccines in pregnant women in VAERS, 2010-2014Safety of Tdap in pregnancy with focus on repeat doses Major birth defects after vaccination reported to VAERS, 1990-2010

Expected output Project lead Type of activity vaccine safety Location United States of America Activity start Activity end Implementing organization



Maria Cano

Source of funding


Activity Identification Evidence generation Activity title Pregnancy Tdap administration Activity objective Identify rates of Tdap administration following recommendation of

vaccination during pregnancy. Ascertain pregnancy outcomes following immunization


This is chart review project looking at the adherence to the recommendation including vaccination and timing. Additionally, the maternal and infant charts are being reviewed to identify outcomes.

Expected output Journal publication Project lead Berenson Type of activity analysis of pregnancy outcomes Location United States of America Activity start 11/1/2012 Activity end 10/31/2016 Implementing organization

University of Texas Medical Branch


Alan Barrett

Source of funding self funded


Activity Identification Evidence generation Activity title literature review of influenza incidence in pregnancy Activity objective To conduct a systematic literature review to better understand

the incidence of influenza in pregnancy Activity description

As part of the WHO Task Force to evaluate influenza data to inform vaccine impact and economic modeling, we will look to gather evidence on the following topics:• Incidence of laboratory-confirmed influenza among pregnant women• Incidence of laboratory-confirmed hospitalized influenza and severe influenza-associated ARI among pregnant women• Incidence of laboratory-confirmed influenza-associated mortality among pregnant women• Disability-adjusted life years lost among pregnant women with laboratory-confirmed influenza

Expected output Report and possible publication Project lead Mark Katz Type of activity systematic literature review -- disease trends Location All countries Activity start 2/6/2015 Activity end Implementing organization

WHO


Mark Katz



Activity Identification Evidence generation Activity title Southern Africa mother infant pertussis study Activity objective To determine the efficacy of maternal Tdap in third trimester for

reducing severe and non-severe infant pertussis. Activity description

Blinded, multi center randomized controlled trial

Expected output Publications Project lead Christopher J. Gill, Saad Omer, Shabir Madhi Type of activity Vaccine effectiveness Location Pakistan,South Africa,Zambia Activity start 2/24/2015 Activity end 2/21/2018 Implementing organization

Boston University


Christopher Gill



Activity Identification Evidence generation Activity title HIV-1 evolution and functionnal correlates of MTCT Activity objective Mother-to-child HIV-1 transmission (MTCT) through breastfeeding Activity description

Mucosal transmission of HIV involves a strong bottleneck effect and most often, a single founder virus is transmitted. The relative contributions of stochastic (random) selection vs. active selection by specific viral and host characteristics to this bottleneck are unclear. Mother-to-child HIV-1 transmission (MTCT) through breastfeeding, in which transmission pairs and timing of infant infection are readily identified, provides an instructive model to address these important and unresolved questions. We will use serial samples from a large, well characterized cohort of HIV-1 infected Zimbabwean women who transmitted HIV-1 through breastmilk. This cohort includes women with chronic HIV-1 infection (CI; N=35), and women who acquired primary HIV-1 infection post-partum (acute infection, AI; N=13). We combine phylogenetics (with frequency analyses based on deep sequencing data) with functional assays (CD4 and co-receptor use, entry kinetics, neutralization sensitivity), to quantitatively and comprehensively analyze the relationship of founder viruses to maternal blood or breastmilk variants,

Expected output Publication Project lead Katherine F. Luzuriaga Type of activity Analysis of disease trends Location Zimbabwe Activity start 2/9/2012 Activity end 1/31/2017 Implementing organization

Univesity of Massachusetts, Medical School Worcester


Opendra K. Sharma



Activity Identification Evidence generation Activity title A novel HIV-1-neutralizing protein isolated from breast

milk Activity objective This work will define the mechanism and efficacy of this newly-

identified HIV-1-neutralizing protein isolated from breast milk, establishing a novel, safe prophylactic agent to protect infants against HIV-1 acquisition via breastfeeding.


we will explore the interactions of this novel HIV-neutralizing protein with the HIV-1 Envelope, defining its active site and the neutralizing epitope of the HIV-1 Envelope that mediates the virus inhibition, potentially uncovering a unique target for HIV-1 neutralization. Furthermore, we will investigate the in vivo efficacy of this protin by investigating the association between the endogenous concentration in milk and protection against postnatal HIV-1 transmission in a large cohort of HIV-infected mother-infant pairs.

Expected output Publication Project lead Sallie R. Permar Type of activity Analysis of disease trends Location All countries Activity start 2/1/2013 Activity end 1/31/2016 Implementing organization

Duke University


Elizabeth H. Stansell




vaccine trial

Expected output publications Project lead Ross Andrews Type of activity Maternal pneumococcal vaccine trial Location Australia Activity start 1/1/2010 Activity end 1/1/2015 Implementing organization

Menzies School of Health Research


Ross Andrews

Source of funding NHMRC


Activity Identification Evidence generation Activity title Effectiveness of trivalent inactivated influenza maternal

vaccination among pregnant women and their newborns in South Africa

Activity objective 1. Primary: To determine the effectiveness of antenatal maternal

influenza vaccination against laboratory-confirmed influenza-associated hospitalised illness in infants


To address the primary and secondary outcomes we will conduct an unmatched test-negative case-control study in 4 sites linked to large hospitals in two provinces of South Africa (Chris Hani-Baragwanath Hospital, Rahima Moosa Mother & Child Hospital and Charlotte Maxeke Johannesburg Academic Hospital in Gauteng Province and Red Cross Children’s Hospital, Tygerberg Hospital, Karl Bremer Hospital, Khayelitsha Hospital, Victoria Hospital and Mitchell’s Plain Hospital in Cape Town). We will conduct a vaccination campaign in antenatal clinics targeting pregnant women before the influenza season and estimate coverage by dividing the number of vaccines delivered by the target population. Active surveillance will be conducted for hospitalised children

Expected output Peer reviewed publication Project lead Cheryl Cohen and Shabir Madhi Type of activity Vaccine effectiveness analysis Location South Africa Activity start 4/1/2015 Activity end 12/31/2017 Implementing organization

Centre for Respiratory Diseases and Meningitis (CRDM), National Institute for Communicable Diseases (NICD) and Respiratory and Meningeal Pathogens Research Unit University of the Witwatersrand


Cheryl Cohen

Source of funding US CDC and Bill & Melinda Gates Foundation


Activity Identification Evidence generation Activity title AEFI surveillance Activity objective To verify and monitor adverse effect following immunization

(AEFI). Activity description

Notification of AEFI by all health facilities and personnel. Lay and media reports are included. Surveillance and Rapid Response Teams (SRRTs) are deployed to investigate reported cases of severe AE. An authorized expert group will scrutinize information and data collected by the investigation team to determine AEFI association with vaccination. (The activity is ongoing since its start about two decades ago, the Activity start date given below is approximate and Activity end date is filled out just to fulfill survey format.)

Expected output Surveillance report. Investigation report. Report of expert group

meeting. These reports are internal, can be accessed on request. Project lead Director, Bureau of Epidemiology, Department of Disease Control,

Ministry of Public Health, Thailand Type of activity special surveillance. Location Thailand Activity start 1/1/1995 Activity end 12/31/2014 Implementing organization



Dr Tanarak Plipat

Source of funding Ministry of Public Health / National budget


Activity Identification Evidence generation Activity title Exploration of protective immunity induced by Salmonella

COPS: FLiC Conjugates Activity objective The purpose of this application is to investigate the

immunogenicity and protective efficacy of COPS:FliC vaccines in a mouse model of maternal and early life immunization.


Exploration of protective immunity induced by Salmonella COPS: FLiC Conjugates

Expected output Publication Project lead Raphael Simon Type of activity analysis of disease trends Location All countries Activity start 8/15/2014 Activity end 7/31/2018 Implementing organization

University of Maryland Baltimore


William A. Alexander



Activity Identification Evidence generation Activity title Effectiveness of influenza vaccination of pregnant women

in protecting against influenza associated hospitalization in young HIV-exposed and HIV-unexposed infants: a case control study

Activity objective The primary objectives of this proposal will include:1. Evaluation

of effectiveness of influenza vaccination of pregnant women against PCR-confirmed influenza illness hospitalization in HEU infants up to 24 weeks of chronological age, who were born at ≥34 weeks of gestational age or birth weight of ≥2500 grams to women that were eligible to have received IIV during the influenza campaign.2. Evaluation of effectiveness of influenza vaccination of pregnant women against PCR-confirmed influenza illness hospitalization in HUU infants up to 24 weeks of chronological age, who were born at ≥34 weeks of gestational age or birth weight of ≥2500 grams to women that were eligible to have received IIV during the influenza campaign.Secondary objectives will include:1. Evaluation of effectiveness of influenza vaccination of pregnant women against PCR-confirmed influenza illness hospitalization in all infants up to 24 weeks of chronological age, who were born at ≥34 weeks of gestational age or birth weight of ≥2500 grams to women that were eligible to have received IIV during the influenza campaign.2. Evaluation of effectiveness of influenza vaccination of pregnant women against PCR-confirmed influenza illness hospitalization in all infants up to 24 weeks of chronological age, irrespective of gestational age or birth weight, born to women that were eligible to have received IIV during the influenza campaign.3. Evaluation of effectiveness of influenza vaccination of pregnant women against all-cause infant mortality (post-discharge from neonatal nursery) up to 24 weeks of chronological age during the duration of the influenza season. 4. Determination of effectiveness of influenza vaccination of pregnant women against PCR-confirmed influenza illness requiring hospitalization or any other medically attended illness during pregnancy and up to 24 weeks post-partum.5. Evaluation of effectiveness of IIV vaccination of pregnant women against fetal outcomes of: i) preterm birth; ii) small for gestational age; iii) birth weight; and iv) stillbirths occurring during the influenza season and up to three months after the end of the influenza season.


This activity aims to increase the coverage of trivalent inactivated influenza vaccination to pregnant women in Soweto, South Africa, to at least 50% during the course of the next 3-years (2015-2017). This would provide an opportunity to address some of the remaining questions with regard to influenza vaccination of pregnant women, which could help advocate for further investment on the part of the government to improve coverage in this high-risk group. In tandem with supporting the increased availability of influenza vaccination to pregnant women in Soweto (estimated 22 500 of whom will be pregnant at any given time-point in the year) we propose undertaking a health care facility


based case-control study during 3 influenza seasons to address specific objectives described above.

Expected output Scientific article Project lead Shabir A Madhi Type of activity vaccine effectiveness Location South Africa Activity start 4/1/2015 Activity end 12/31/2017 Implementing organization

Wits Health Consortium


Marta Nunes



Activity Identification Evidence generation Activity title Gut microflora: impact on neonatal immunity, viral

gastroentiritis and vaccines Activity objective Address gaps in knowledge of gut immune maturation and

homeostasis and interactions between gut microflora and enteropathogenic viruses or oral vaccines. select probiotics/commensals modulating gut homeostasis and immune responses and impact enteric diseases and vaccines. this will permit their rational use as biotherapeutic agents and/or adjuvants.


We hypothesize that selected G+ and G- gut microflora will modulate different host cellular pathways leading to immunostimulatory, but balanced (Th1/Th2/Th17/Treg) responses that enhance efficacy of RV vaccines or immuno-regulatory (Treg) responses that moderate HRV diarrhea. Further, humanized, outbred Gn pigs are a unique model to study how microbiota and diet contribute to malnutrition and HRV disease severity under conditions that constrain confounding variables in ways not possible in infants. In Aim 1, we determine how selected G+ or G- probiotics, both, or the commensal cocktail modulates immune responses, gut homeostasis and HRV pathogenicity. Then we test the impact of antibiotics on the commensal microflora and on these same parameters. In Aim 2, we determine how defined probiotics or commensals modulate protective immunity to AttHRV oral vaccine. In Aim 3, in collaboration with Jeff Gordon, we develop a humanized Gn pig model to study the interaction of microbiota x diet (from African twins discordant for kwashiorkor) on severe malnutrition and HRV pathogenicity and identify microbial biomarkers to aid in vaccine design or therapeutic interventions. Effects of the probiotics/commensals/microbiota will be compared by intestinal transcriptome profiling (pig microarrays, 44K ESTs), metagenomics, metabolomics and metatranscriptomics, gut barrier integrity (sugar permeability, tight junction genes, serum LPS), and induction of innate and adaptive immune responses, to establish the immunoregulatory/immunostimulatory profiles. Our findings will contribute to alternative low cost probiotic treatments applicable to infants (or mothers) to moderate HRV disease, enhance oral vaccine efficacy, and reduce infant morbidity and mortality.

Expected output Publication Project lead Gireesh Rajashekara ,Anastasia N. Vlasova Type of activity Analysis of disease trends Location All countries


Activity start 6/1/2012 Activity end 5/31/2017 Implementing organization

Ohio State University


Melody Mills



Activity Identification Evidence generation Activity title Safety and immunogenicity of anti-pneumococcal vaccines

in HIV-infected pregnant women: NICHD P1091 Activity objective Primary:1. To evaluate the safety of the PCV-10 and PPV-23

vaccines in HIV-infected pregnant women on HAART.2. To compare the immunogenicity of PCV-10 with PPV-23 vaccines in HIV-infected pregnant women on HAART.3. To compare the level of anti- Pneumococcal (PNC) antibodies at 8 weeks of life in infants born to mothers who received PCV-10 or PPV-23 vaccines.Secondary:1. To compare the level of transplacentally transferred vaccine-serotype anti-PNC antibodies in infants born to mothers who received PCV-10 or PPV-23 versus placebo. 2. To compare the immunogenicity of PCV-10 and PPV-23 vaccines with placebo in HIV-infected pregnant women on HAART.3. To compare the persistence of vaccine-serotype PNC anti-capsular antibodies for up to 24 weeks after delivery in HIV-infected women vaccinated with PCV-10, PPV-23, or placebo.4. To compare maternal antibody responses to PPV-23 or PCV-10 administered during pregnancy with responses to PPV-23 or PCV-10 administered 24 weeks postpartum.5. To evaluate the effect of the following factors on the magnitude and persistence of the maternal antibody responses to PCV-10 and PPV-23: maternal age, ethnicity, CD4, CD8, plasma HIV Ribonucleic Acid (RNA) and gestational age at immunization.6. To assess potential interference of maternal antibodies with infant vaccine-serotype PNC anti-capsular antibody responses after each dose of PCV-10 and determine if interference of maternal antibodies differs in PCV-10 from PPV-23 and from placebo recipients.


DBPC

Expected output Publication Project lead Adriana Weinberg, MD Type of activity Vaccine study Location Brazil Activity start 11/1/2015 Activity end 11/1/2017 Implementing organization

WESTAT


Adriana Weinberg


Source of funding NICHD


Activity Identification Evidence generation Activity title Surveillance of vaccine preventable diseases Activity objective to monitor the occurrence of communicable diseases, including

vaccine preventable diseases (VPDs), as well as other major health hazards.


reporting of notifiable diseases. 84 items of diseases and health hazards are included in disease notification system. The notifiable diseases include 15 VPDs (influenza, chickenpox, hepatitis, mumps, typhoid, measles, rubella, tetanus, Japanese encephalitis, diphtheria, pertussis, meningcoccal meningitis, rabies, poliomyelitis and tuberculosis). Reports of individual cases of the notifiable diseases are submitted by public sector health facilities countrywide, to respective provincial health offices, and finally collected and analyzed by Bureau of Epidemiology, Department of Disease Control, Ministry of Public Health.

Expected output weekly report, annual report. weblinks: 1)

http://www.boe.moph.go.th/index.php?nphss=nphss and 2) http://www.boe.moph.go.th/Annual/AESR2013/

Project lead Director, Bureau of Epidemiology, Department of Disease Control,

Ministry of Public Health, Thailand Type of activity Surveillance report Location Thailand Activity start 1/1/1968 Activity end 12/31/2014 Implementing organization



Dr Tanarak Plipat



Activity Identification Evidence generation Activity title B cell immunity in HIV exposed uninfected infants in Kenya Activity objective The long term consequences of fetal exposure to maternal

dysregulated chronic immune activation. Activity description

several reports of HIV EU infants examined beyond the neonatal period show persistently activated T cell populations, higher levels of polyclonal antibodies, and increased B cell apoptosis compared to infants of HIV- mothers. prenatal exposure to the chronically activated maternal immune environment resulting from HIV infection modulates fetal immune development and the subsequent development of infant immunity to childhood vaccines among African infants. To test this hypothesis, we will examine the development of B cell immunity in Kenyan HIV EU infants compared to non HIV exposed infants. Specifically, we will examine infants from birth to 2 years of age focusing on characterizing B cell subsets

Expected output publication Project lead Arlene Dent Type of activity analysis of disease trends and vaccine effectiveness Location All countries Activity start 7/1/2012 Activity end 6/30/2016 Implementing organization

Case Western Reserve University


Opendra K. Sharma



Activity Identification Evidence generation Activity title Vaccines and maternally acquired immunity to prevent

Shigellosis in children Activity objective Uncover a new mechanism involved in protection against

shigellosis and a more effective vaccine approach for the protection of children after the waning of maternal immunity.


Using transgenic mice expressing the human FcRn we will examine the transLocation and protective capacity of IgG in human breast milk. We will investigate OPA and SBA capacity of Shigella-specific IgG in vaccine recipients and their association with reduced severity of disease. We will also measure kinetics of maternally acquired antibodies in a longitudinal study involving mothers and their infants (followed up to 2 years of age) living in endemic regions. Lastly, using a human enteroid model, we will dissect the components of maternal milk that prevent Shigella infection; particularly FcRn-mediated intestinal transLocation of breast milk IgG. We will investigate a novel strategy that combines CVD1208S (a live attenuated vaccine) with the invasion plasmid antigen IpaD (a highly conserved type III secretion protein), and the Escherichia coli double mutant heat labile enterotoxin (dmLT) to induce broad protection and strong, long lasting immunity.

Expected output publication Project lead Marcela F. Pasetti Type of activity Aanalysis of disease trends Location All countries Activity start 2/1/2015 Activity end 1/31/2012 Implementing organization

University of Maryland Baltimore


Melody Mills



Activity Identification Evidence generation Activity title H1N1 Immunization during pregnancy and adverse

pregnancy and infant outcome Activity objective To evaluate risks associated with H1N1 immunization in Sweden

performed in 2009-2010 Activity description

We investigate risk of adverse pregnancy and infant outcome associated with immunization for H1N1 in Sweden 2009-2010. We have linked national register data with H1N1 vaccination data. We used the medical birth register, the patient register and the cause of death register for follow-up.

Expected output We have published one article in E J Epidemiology:

http://www.ncbi.nlm.nih.gov/pubmed/23715672 Project lead Professor Jonas F Ludvigsson, Karolisnka Institutet, Stockholm

Sweden Type of activity Research in adverse pregnancy and infant outcome in women

vaccinated for H1N1 during pregnancy Location Sweden Activity start 1/1/2013 Activity end 12/31/2015 Implementing organization

Karolinska Institutet, Stockholm, Sweden


Olof Stephansson

Source of funding The Swedish Research Council and the Swedish Council for

Working Life and Social Research


Activity Identification Evidence generation Activity title Safety of pertussis vaccination in pregnant women Activity objective To monitor the safety of pertussis-containing vaccines in pregnant

women Activity description

In 2012, following an increase in the number of confirmed cases of pertussis and a number of infant deaths, the UK introduced a new temporary vaccination program targeting pregnant women in their third trimester. This cohort study using the UK Clinical Practice Research Datalink was designed to look at a range of pregnancy related events of interest following vaccination with a pertussis containing vaccine and compare these rates to those seen in a historical cohort of unvaccinated women. This study reported in July 2014 on the safety of Repevax in pregnancy and continues due to change in the vaccine brand being used in the program.

Expected output 1st report: http://www.bmj.com/content/349/bmj.g4219 Project lead Dr Katherine Donegan Type of activity Vaccine safety Location United Kingdom of Great Britain and Northern Ireland Activity start 10/1/2012 Activity end Implementing organization

Medicines and Healthcare products Regulatory Agency (MHRA)


Katherine Donegan

Source of funding


Activity Identification Evidence generation Activity title Safety of human papillomavirus vaccination in pregnancy Activity objective Activity description

HPV vaccination is not licensed for use in pregnancy. However, in cases of early pregnancies yet to be discovered, inadvertent vaccinations do occur. This study will take advantage of the unique nationwide Danish registers to study the safety of HPV vaccination in pregnancy.

Expected output Journal paper Project lead Anders Hviid Type of activity Vaccine safety Location Denmark Activity start 6/1/2015 Activity end 5/31/2016 Implementing organization

Statens Serum Institut, Copenhagen.


Anders Hviid

Source of funding Novo Nordisk Research Foundation.



Activity title Develop commentary on maternal immunization and pregnancy outcome

Activity objective Consider methodological issues in epidemiologic studies examining the potential benefit of influenza vaccination and pregnancy outcome, particularly preterm birth. This will apply to the interpretation of past studies and the design of new studies on this topic.


I am collaborating with Niranjan Bhat to develop a commentary that we plan to submit for publication in a peer-reviewed journal.

Expected output Publication

Project lead David A savitz

Type of activity Consideration of influenza vaccination and pregnancy outcome




David A Savitz


David A Savitz

Source of funding World Health Organization


Activity Identification Evidence generation Activity title Pertussis immunisation in pregnancy— infant outcomes

(PIPIO) tudy Activity objective Evaluated the effectiveness of maternal immunisation in

preventing or reducing the severity of pertussis disease outcomes in the infant


An epidemiological study using data linkage of existing administrative health databases to evaluate the effectiveness of fetal exposure to maternal pertussis vaccine against pertussis disease in infancy

Expected output Conference presentations, academic publications Project lead Helen Petousis-Harris Type of activity Vaccine effectiveness Location New Zealand Activity start 7/1/2014 Activity end 6/30/2015 Implementing organization

University of Auckland


Helen Petousis-Harris

Source of funding New Zealand Health Research Council in Partnership with Ministry

of Health


Activity Identification Evidence generation Activity title Clinical Research in Infectious Diseases (CRID) Activity objective Provide statistical and data management support to clinical trials

conducted through Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health


This activity includes safety follow-up of women who become pregnant post-administration of experimental vaccines, including the vaccine for seasonal influenza. Although women who are pregnant or plan to become pregnant are typically excluded from CRID trials, a Pregnancy Outcome form has been developed to capture safety outcomes in women who become pregnant after product administration and in their infants. Safety data collected include maternal complications, infant gestational age and measurements, infant Apgar scores, illness or congenital anomalies in newborns, product of conception abnormalities in miscarriages and abortions, and autopsy results in stillbirths. We have also participated in vaccine clinical trials in influenza, pertussis, and schistosomiasis that seek to investigate the safety and immunogenicity of the vaccines in pregnant women and their children.

Expected output Data in support of vaccine development Project lead Marian Ewell, ScD Type of activity Vaccine safety and immunogenicity Location Philippines,United States of America Activity start 3/1/2008 Activity end 2/28/2022 Implementing organization

Emmes


Heather Hill, MS

Source of funding Division of Microbiology and Infectious Diseases, National

Institute of Allergy and Infectious Diseases, National Institutes of Health



Activity title Concurrent and Cross-Season Protection of Inactivated Influenza Vaccine against A(H1N1)pdm09 Illness among Young Children: 2012-13 Case-control Evaluation of Influenza Vaccine Effectiveness

Activity objective To evaluate the field VE of 2012-13 Northern Hemisphere IIV3 and to examine the relative protective value of full vs. partial influenza vaccination and the duration of protection afforded by IIV3 among children aged 8 months to 6 years old .


In 2012-13, we examined 1,729 laboratory-confirmed A(H1N1)pdm09 influenza cases matched 1:1 with healthy controls and estimated influenza vaccine effectiveness (VE) for trivalent inactivated influenza vaccine (IIV3) to be 67% (95% confidence interval = 58-74%) for ages 8 months to 6 years old. Among children aged 8-35 months old, VE for fully vaccinated children (73%, 60-81%) was significantly higher than VE for partially vaccinated children (55%, 33-70%). Significant cross-season protection from prior IIV3 was noted, including VE of 31% (8-48%) from IIV3 received in 2010-11 against influenza illness in 2012-13 without subsequent boosting doses.

Expected output Manuscript basically accepted by Vaccine

Project lead Chuanxi Fu

Type of activity Vaccine effectiveness

Location China





Chuanxi Fu

Source of funding Guangzhou Center for Disease Control and Prevention


Activity Identification Evidence generation Activity title Therapeutic antibodies for CMV Activity objective Test sub-nanomolar affinity native human mAb against HCMV

glycoprotein B (gB) Activity description

CMV345, mAb for blocking infection of the placenta, reducing the early pathogenic effects of virulent strains on placental development, and preventing virus transmission at the uterine-placental interface, is a promising candidate for passive immune therapy to replace and improve upon HIG. CMV345 for clinical testing: the Phase I proof of concept, Phase II studies IND-enabling manufacturing andon further elucidation of the mechanism of action needed to design the clinical strategy.

Expected output Publication Project lead Lawrence Kauvar Type of activity Vaccine effectiveness Location All countries Activity start 8/1/2012 Activity end 1/31/2016 Implementing organization

TRELLIS BIOSCIENCE, LLC


Christopher E. Beisel



Activity Identification Evidence generation Activity title Pertussis in pregnancy safety (PIPS) study: A three-

component observational study to assess the safety of pertussis vaccine (Tdap) administered during pregnancy

Activity objective To evaluate health outcomes in infants of mothers vaccinated

with Tdap during pregnancy and describe adverse events in pregnant women who received Tdap vaccine.


Whole birth cohort (Study One)To establish background rates for key endpoints in pregnant women and their infants• Secondary objective 1: To examine the difference in hospital-related outcomes of those vaccinated or not with Tdap during pregnancy in all NZ women pregnant between 2009 and 2013.• Secondary objective 2: To examine the difference in birth outcomes and hospital-related outcomes of infants born to mothers vaccinated or not with Tdap during pregnancy in all NZ women pregnant between 2009 and 2013.Intensive safety monitoring (Study Two)To intensively follow up a subgroup of NZ women who received pertussis-containing vaccine, during pregnancy for a period of one month after vaccine administration and document health outcomes for vaccinees for this period.Intensive safety monitoring (Study Three) Canterbury District Health Board (DHB)To describe adverse events in women who were administered Tdap under the DHB programme between 30–36 weeks of gestation To describe outcomes of babies whose mothers were vaccinated with Tdap in the Canterbury region during week 30 to 36 of pregnancy (including birth history, weight and head circumference and any congenital abnormalities

Expected output Conference presentations, Academic publications Project lead Helen Petousis-Harris Type of activity Vaccine safety Location New Zealand Activity start 12/3/2013 Activity end 1/21/2016 Implementing organization

University of Auckland


Helen Petousis-Harris

Source of funding GSK BIO


Activity Identification Evidence generation Activity title THE ROLE OF ANTIBODIES IN MOTHER TO CHILD HIV

TRANSMISSION Activity objective Define humoral immune correlates of protection against HIV

infection Activity description

We will capitalize on a large clinical trial of MTCT - the Nairobi Breastfeeding Clinical Trial - that enrolled several hundred HIV positive pregnant women and followed them from the third trimester through 2 years of life in the infant. Here we propose to utilize this unique large cohort with regular sample collection and detailed data on infant infection to examine the role of both maternal and infant ADCC in MTCT

Expected output Publication Project lead Juliem Overbaugh Type of activity Analysis of disease trends Location Kenya Activity start 3/1/2008 Activity end 5/31/2018 Implementing organization

Fred Hutchinson Cancer Research Center


Judith A. Miller



Activity Identification Evidence generation Activity title Activity objective Set the standard for the type of mucosal antibody responses that

an effective HIV-1 vaccine should target. Define the mucosal HIV-1 Env-specific IgG and IgA antibody responses that can protect against HIV-1 transmission to infants via breastfeeding, establishing the maternal antibody responses required to eliminate postnatal HIV-1 transmission.


We will contrast the genetc characteristics and epitope-specificity of HIV-1 Env-specific antibodies produced by systemic and mucosal B cells isolated from a repository of breast milk and peripheral blood mononuclear cells of HIV-1-infected women; 2) identify qualities and epitope-specificities of mucosal HIV-1 Env-specific IgG and IgA antibodies that possess potent in vitro neutralizing and nonneutralizing functions that may block HIV-1 transmission; and 3) determine the ability of mucosally-produced HIV Env-specific IgG and IgA antibodies to protect against virus acquisition in vivo, using the neonatal rhesus monkey/oral simian-HIV (SHIV) transmission model.

Expected output Publication Project lead Sallie R. Permar Type of activity Analysis of disease trends Location All countries Activity start 5/22/2013 Activity end 4/30/2018 Implementing organization

Duke University


Vijay L. Mehra



Activity Identification Evidence generation Activity title Safety of Influenza Vaccination in Pregnancy Activity objective Activity description

Register-based epidemiological research on adverse effects of influenza vaccination in pregnancy. This includes the study of birth defects, adverse birth outcomes such as fetal death and childhood health.

Expected output Journal papers. Project lead Anders Hviid Type of activity Vaccine safety Location Denmark Activity start Activity end Implementing organization

Statens Serum Institut, Copenhagen.


Anders Hviid

Source of funding Various


Activity Identification Evidence generation Activity title FluMum: A prospective cohort study of mother-infant pairs

assessing the effectiveness of maternal influenza vaccination in prevention of influenza in early infancy

Activity objective Determine the effectiveness of maternal influenza vaccine in

pregnancy using laboratory confirmed influenza results among infant offspring during the first 6-months of life.


Multi national, multi centred observational trial studying the effectiveness of maternal influenza immunisation in infants up to 6 months of age. The aim is to recruit about 420 women in Australia in each site each year so that, after 4 years, we expect to have just over 10,000 women and their babies who are part of the study. There are six sites: Darwin, Brisbane, Sydney, Melbourne, Adelaide and Perth.Recruitment will be through ante-natal care providers, maternity units within participating hospitals or through clinics providing routine postnatal services at 6 weeks post delivery in Darwin, Brisbane, Sydney, Melbourne, Adelaide and Perth. The study will be explained to potential participants utilising a Plain Language Statement approved by the relevant Human Research Committee (HREC). The study is aimed at mothers immunised against Influenza in the 12 months prior to the birth of their infant. The vaccine must not have been given =

Expected output Project lead A/Professor Ross Andrews Type of activity Effectiveness, uptake. Location Australia Activity start 3/22/2012 Activity end Implementing organization


Source of funding National Health & Medical Research Council Project Grant


Activity Identification Evidence generation Activity title Safety of Post-exposure Rabies prophylaxis during

pregnancy: a follow-up study from China Activity objective To assess the safety profile of post-exposure prophylaxis (PEP)

for rabies in pregnant women Activity description

All of the subjects received the Essen vaccination regimen. Systemic and local reactions were monitored within 72 hours following the immunization, and the subjects were followed until six months after delivery. No moderate or severe adverse effects occurred in any subject following the vaccination. Among the 72 subjects in this follow-up study, four had voluntary abortions, one subject had an accidental miscarriage, and the remaining 67 subjects delivered babies vaginally or by caesarean section. All of the infants exhibited normal development.The purified Vero cell rabies vaccine and the purified chick embryo cell vaccine were both safe for the PEP of pregnant women and did not interfere with the development of the fetuses or infants. Education is needed in China to stop pregnancy terminations due to concerns about rabies vaccination risk.

Expected output http://www.ncbi.nlm.nih.gov/pubmed/23442589 Type of activity Guihua Huang Project lead Vaccine safety Location China Activity start 1/1/2009 Activity end 6/30/2009 Implementing organization



Chuanxi Fu

Source of funding Guangzhou Center for Disease Control and Prevention


Activity Identification Evidence generation Activity title Optimising protection for pregnant women with influenza

vaccination Activity objective To determine whether there is any relationship between BMI and

the effectiveness of influenza vaccination in pregnant women. Activity description

Approximately 300 pregnant women will be enrolled in this study at the Women’s and Children’s Hospital over two influenza seasons. Whilst recruitment will not be targeting any specific BMI of potential participants, we expect that approximately 150 obese and non-obese participants will be enrolled. This is a prospective cohort study including obese and non-obese pregnant women to assess difference in seroprotective status after a seasonal influenza vaccination given according to standard practice. All pregnant women will be administered 1 (0.5ml) dose of the licensed influenza vaccine into the upper deltoid muscle of the arm. Group 1: Participants with a BMI >=30kg/m2 Group 2: Participants with a BMI

Expected output Published Type of activity Helen Marshall Project lead Efficacy Location Australia Activity start 4/1/2014 Activity end 12/31/2015 Implementing organization

VIRTU


Source of funding SA Health


Activity Identification Evidence generation Activity title Research, monitoring and outcomes definitions for vaccine

safety Activity objective Conducting research on vaccine safety with a special interest in

measuring vaccine safety in pregnant women and newborns after maternal immunization administration


The program’s objective is to conduct research in vaccine safety related areas, specifically, but not limited to, determining the safety profile of new vaccines during the early development stage, developing or modifying existing vaccines to improve their safety, conducting applied research that will have a direct impact on the current vaccine safety monitoring system, conducting research that will achieve consensus definitions of vaccine safety outcomes that could be utilized to collect consensus data in clinical research conducted globally. The National Vaccine Program Office is particularly interested in projects related to researching, establishing or testing the vaccine safety profile of vaccines that are currently recommended for or are expected to be routinely administered to pregnant women and/or newborns. Topics of research may cover establishing the safety of a vaccine in either the pregnant women, her newborn or both, at any stage of the vaccine development, testing and/or pre-clinical or clinical research and monitoring of vaccine safety.

Expected output Publication Project lead Dr. Bruce Gellin, Dr. Karin Bok Type of activity Coopertative Agreement Location United States of America Activity start 7/1/2015 Activity end 6/30/2016 Implementing organization

National Vaccine Program Office, Office of the Assistant Secretary for Health, Department of Health and Human Services, US


Dr. Karin Bok

Source of funding Federal Budget


Activity Identification Evidence generation Activity title Activity objective Mother-to-child transmission (MTCT), to study the role of pre-

existing antibodies in protection: Infants receive passively transferred HIV-specific antibodies in utero that may protect against infection during breastfeeding.


This proposal utilizes a unique cohort of HIV-positive mothers and their infants from Nairobi, Kenya conducted from 1992 to 1998. The infants to be studied were all uninfected at birth but continually exposed to the virus via breastfeeding, and thus at risk for infection. Using this cohort, we will focus on th role of Fc-mediated antibody responses in MTCT. One such response is antibody-dependent cellular cytotoxicity (ADCC), which has been shown to influence HIV-1 acquisition and disease progression in macaques and humans. This study will address the hypothesis that ADCC activity mediated by passively acquired antibodies is inversely correlated with risk of infection i infants born to HIV-positive mothers. cells bearing the FcR genotype(s) of the infant. Overall, these studies will provide knowledge on the role of pre-existing ADCC antibodies and host genetics in MTCT. These data will help inform future vaccine studies and provide insight into host factors that may influence vaccine effectiveness.

Expected output Publication Project lead Caitlin E. Milligan Type of activity Analysis of disease trends Location Kenya Activity start 4/1/2014 Activity end 9/30/2016 Implementing organization



Judith A. Miller



Activity Identification Evidence generation Activity title Collection of biological material from pregnant women in

malarial region Activity objective Collection of biological material from pregnant women and infants Activity description

In vitro evalaution of anti-adhesion activity by antibodies to pregnancy malaria vaccien candidates.

Expected output publication Project lead Michal Fried Type of activity vaccine efficacy Location Uganda Activity start 2/1/2013 Activity end 3/1/2017 Implementing organization

National Institute of Health Clinicla Center


Michal Fried



Activity Identification Evidence generation Activity title Group B Stretpococcus (GBS) and Respiratory Syncytial

Virus (RSV) Activity objective Evidence generation for maternal vaccination to protect infants

from invasive GBS disease and RSV infection through transplacental transfer of protective antibodies


-Clinical Development Program advancing a conjugated GBS Trivalent Vaccine to be administered to pregnant women to protect their newborns from invasive GBS disease. -Clinical Development Program advancing a Recombinant RSV F Subunit Vaccine to be administered to pregnant women to protect their newborns from RSV disease

Expected output Evidence of safety and efficacy of GBS and RSV vaccine in

mothers and infants Project lead GlaxoSmithKline Vaccines (formerly Novartis Vaccines) Type of activity Vaccine effectiveness/efficacy Location All countries Activity start 1/1/2010 Activity end Implementing organization

GlaxoSmithKline Vaccines (formerly Novartis Vaccines)


Alexandra Mangili, MD, MPH

Source of funding GlaxoSmithKline Vaccines (formerly Novartis Vaccines)


Activity Identification Evidence generation Activity title Field Testing of functional activity by pregnancy malaria

vaccine candidtes Activity objective Identify the best domain or domain combination as an alternative

to the full length protein for malaria vaccine during pregnancy . Activity description

VAR2CSA is the leading candidate for a PM vaccine. Because the protein encoded by var2csa is a large molecular weight protein (m.w.300 kD) consisting of 6 DBL domains, major effort by numerous labs focused on identifying the best domain or domain combination as an alternative to the full length protein. Using functional genomic tools, additional conserved protein named PfCSA-L (encoded by the gene PF10_0013) was identified as a PM vaccine candidate. Like VAR2CSA, the protein is expressed on the surface of IE and a recombinant form of the protein binds to CSA. These data establish VAR2CSA and PfCSA-L as leading candidates for inclusion in a pregnancy malaria vaccine.

Expected output Publication Project lead Michal Fried Type of activity Vaccine effectivness Location All countries Activity start Activity end Implementing organization

National Institute of allergy and infectious diseases




Activity Identification Evidence generation Activity title Evaluating the response to three antiretroviral medication

regiments in HIV infected pternant women who begin antiretroviral therapy btween 28 and 36 weeks of pregnancy for prevention of mother-to-child transmission

Activity objective Viral load decrease sustaniend until delivery; safety, tolerability

and viral suppersison. Activity description

A phase IV randomized trial to evalaute virologic response and PK of three different regiments in HIV infected pregnant women.

Expected output Publication Project lead Mark M. Esau Joao Type of activity Analysis of dieses trend Location All countries Activity start 7/1/2013 Activity end 6/30/2019 Implementing organization

International multicenter trial





Activity title Efficacy of maternal immunization with influenza vaccine in preventing influenza in infants and mothers in Mali, West Africa

Activity objective to estimate incidence of influenza-like illness and lab confirmed influenza in pregnant and post-partum women and their infants and conduct controlled trials to determine safety and effectiveness of maternal flu vaccine for women and their infants


Influenza

Expected output

Project lead

Type of activity

Location Mali



University of Maryland, Baltimore





Activity title Field study in Africa of maternal influenza immunization

Activity objective to support a field study in Africa on maternal influenza immunization in South Africa


Influenza

Expected output

Project lead

Type of activity

Location South Africa








Activity title RSV burden of disease study

Activity objective To support a respiratory syncytial virus burden of disease study


RSV

Expected output

Project lead

Type of activity

Location Argentina



Vanderbilt University





Activity title Maternal influenza immunization: Building an immunization platform in conjunction with antenatal care in low and middle-income countries

Activity objective To assess new sources of data on the safety profile on IIV in pregnant women


Publish a report of the influenza vaccine safety review, endorsed by GACVS

Expected output Influenza vaccine safety review report endorsed by GACVS

Project lead Joachim Hombach

Type of activity Vaccine safety

Location Switzerland, United States





Philipp Lambach



Activity Identification Evidence generation Activity title Group B Streptococcus colonization in mother-newborn

dyads and association with anti-capsular serotype-specific antibodies in low and middle income South Asian and African countries

Activity objective to contribute towards delineating the public-health importance of

invasive Group B Streptococcus (GBS) disease across different low income countries and, particularly, the likely role of GBS as cause of invasive disease during the newborn period


Group B Strep

Expected output Project lead Type of activity Location India, Pakistan, Bhutan, Bangladesh, Indonesia, Nigeria, Mali,

Zambia, Zimbabwe, Mozambique, Malawi, Ethiopia Activity start 10/27/2014 Activity end 11/1/2017 Implementing organization






Activity title Effectiveness of influenza vaccination of pregnant women in protecting against influenza associated hospitalization in young HIV-exposed and HIV-unexposed infants: a case control study

Activity objective to increase the evidence base on the effectiveness of influenza vaccination of pregnant women to protect against severe illness requiring hospitalization among young-infants, including those born to HIV-infected mothers


Influenza

Expected output

Project lead

Type of activity

Location South Africa








Activity title Maternal influenza immunization: building an immunization platform in conjunction with antenatal care in low and middle-income countries

Activity objective To conduct a review of birth outcome data for low resources settings


Expected output Report describing the general process by which WHO can increase the amount of publicly available influenza vaccine safety data in pregnancy by collating and analysing data made publicly available through manufacturer and regulatory databases. Report detailing review of public databases, procedures for systematic analysis, and feasibility of and resources required for completion of such a review.


Type of activity Vaccine safety






Philipp Lambach



Activity Identification Immunization & Financing Policy

Activity title Maternal influenza immunization: Building an immunization platform in conjunction with antenatal care in low and middle-income countries

Activity objective Conduct scientific review and reach a regulatory consensus on data requirements for product labelling of influenza vaccines for pregnant and lactating women


Develop scientific consensus and resulting report on data needs for IIV product labelling concerning their use during pregnancy and lactation

Expected output Scientific consensus and resulting report on data needs for IIV products labeling concerning their use during pregnancy and lactation


Type of activity






Ivana Knezevic, HyeNa Kang




Activity title Acute and long term consequences of RSV infection in children

Activity objective To research the acute and long term consequences of RSV infection in children


RSV

Expected output

Project lead

Type of activity

Location Argentina



Vanderbilt University





Activity title Improving current global estimates of RSV-ALRI morbidity and mortality

Activity objective to improve current global estimates of morbidity and mortality due to RSV–associated acute lower respiratory infections in young children


RSV

Expected output

Project lead

Type of activity

Location United Kingdom



The University of Edinburgh





Activity title Efficacy and Immunogenicity of Tdap immunization of pregnant women for preventing Pertussis in early infancy in Pakistan

Activity objective to develop an evidence base to support widespread policy recommendations for maternal pertussis vaccination during pregnancy


Pertussis

Expected output

Project lead Saad Omer

Type of activity

Location Pakistan, United States



Emory University





Activity Identification Evidence Generation

Activity title Maternal immunization to prevent neonatal deaths due to sepsis and meningitis in GAVI-eligible, sub-Saharan African countries: Cost-effectiveness of group B streptococcal vaccine

Activity objective to analyze the value of maternal vaccination against group B streptococcus in order to help low-income sub-Saharan African countries prevent neonatal deaths


Group B Strep

Expected output

Project lead Anushua Sinha

Type of activity

Location United States



Rutgers University Foundation


Anushua Sinha




Activity title Southern Africa Mother Infant Pertussis Study: Phase I (SAMIPS-1)

Activity objective to measure the burden of severe and non-severe pertussis disease among young African infants in a setting of very high maternal HIV seroprevalence


Pertussis

Expected output

Project lead Christopher J. Gill

Type of activity

Location Zambia, United States



Boston University


Christopher Gill




Activity title Develop biomarkers of RSV disease severity for vaccine trials

Activity objective to develop better quantitative measures of the severity of RSV disease, an important cause of serious lung infections and death in young children globally


RSV

Expected output

Project lead

Type of activity

Location Argentina, United States



Emory University




Activity Identification Evidence generation Activity title Site preparation activities in support of the upcoming

southern Africa mother-infant Pertussis study (SAMIPS) Activity objective To prepare for a site inspection at the Lusaka, Zambia research

site in preparation for activities related to testing whether passive maternal immunity resulting from maternal Tdap will provide an effective bridge between birth and when infants are able to mount their own immune responses to vaccines.


Pertussis

Expected output Project lead Christopher J. Gill Type of activity Location United States, Zambia Activity start 6/2/2014 Activity end 11/30/2015 Implementing organization

Boston University


Christopher Gill



Activity Identification Evidence generation Activity title Pertussis burden of disease study Activity objective To estimate the incidence of severe pertussis-associated

hospitalizations in infants under six months old in Soweto, South Africa


Pertussis

Expected output Project lead Type of activity Location South Africa Activity start 10/1/2014 Activity end 2/29/2016 Implementing organization





Activity Identification Evidence generation Activity title Landscape analysis of maternal pertussis immunization in

low-resource countries Activity objective to conduct a landscape analysis assessing the current knowledge

gaps, operational barriers, and opportunities for implementing antenatal pertussis immunization programs in low-resource countries


Pertussis

Expected output Project lead Type of activity Location United States, Denmark Activity start 8/14/2014 Activity end 1/31/2015 Implementing organization

PATH




Activity Identification Evidence generation Activity title GAIA - Global Alignment of Immunization safety and

assessment in pregnancy Activity objective To improve data generated for strengthening programs of

immunization in pregnancy by harmonizing maternal, pregnancy, fetal, and neonatal health outcome assessment with specific focus on Low and Middle Income Countries (LMIC).


Expected output Project lead Type of activity Location India, Europe, US, Australia Activity start 1/5/2015 Activity end 11/30/2016 Implementing organization

Brighton Collaboration





Activity title Pertussis efficacy studies and vaccine development

Activity objective to increase the evidence base regarding the efficacy of vaccination of women during pregnancy against pertussis, thereby supporting efforts to make available a potentially high-impact intervention to reduce pertussis in mothers and newborns


Pertussis

Expected output

Project lead

Type of activity

Location Zambia, United States, Thailand, South Africa, Pakistan, Denmark



PATH





Activity title Mother'sGift Field Trial

Activity objective To conduct field trial maternal influenza immunization in Asia (Mother’s Gift 241 Field Trial)


Evidence Generation

Expected output

Project lead

Type of activity

Location Kenya, Nepal, Bangladesh



Cincinnati Children's Hospital Medical Center




Activity Identification Evidence generation Activity title Role of pertussis antitoxins (baboon model) Activity objective To support a proof of concept study in a baboon model in order to

determine if maternal vaccination with pertussis toxoid alone is sufficient to confer protection to newborns


Pertussis

Expected output Project lead Type of activity Location United States Activity start 11/25/2014 Activity end 11/25/2016 Implementing organization

Center for Biologics Evaluation and Research, FDA




Activity Identification Policy development Activity title National program on influenza immunization Activity objective To protect high-risk population from influenza morbidity and

mortality Activity description

Provision of influenza vaccine to high-risk population groups. This program has been implemented countrywide since 2008. Target population includes the elderly, people with chronic health conditions, pregnant women (since 2010) and children 6 months to 2 years of age (since 2010). The program is ongoing, and evolving in to an integral part of EPI.

Expected output Program report (internal) Project lead Director, Bureau of General Communicable Diseases, Department

of Disease Control, Ministry of Public Health, Thailand Type of activity Vaccination campaign, annual. Location Thailand Activity start 5/1/2008 Activity end 12/31/2014 Implementing organization

EPI program, Bureau of General Communicable Diseases, Department of Disease Control, Mnistry of Public Health, Thailand


Dr Rungrueng Kitphati



Activity Identification Policy development Activity title Review of influenza burden in children 0-5 months of age Activity objective Review and synthesize available data regarding the incidence of

influenza in infants under 6 months of age Activity description

Literature review and data synthesis

Expected output Written report Project lead Niranjan Bhat Type of activity Evidence review Location All countries Activity start 2/24/2014 Activity end 3/27/2015 Implementing organization

WHO and PATH


Niranjan Bhat



Activity Identification Policy development Activity title Former member of ACIP to CDC (USA); current liaison

member to ACIP from the Infectious Diseases Society of America; member of ACIP work group on pertussis; advisor to BMGF program on maternal immunization

Activity objective Develop evidence-based policy for maternal immunization with

influenza, Tdap and future vaccines (eg, group B Streptococcus, tetanus, RSV)


As a member or advisor to these groups, my prior research in the field of maternal immunization and especially in the field of group B streptococcal (GBS) infections in pregnant women, neonates and young infants, provides background expertise to these various policy-making and research conducting bodies named above (including manufacturers of vaccines for use in pregnant women). While not directly involved in influenza research, the benefit to mother and infant for this viral infection mimics the concepts for GBS.

Expected output Meeting minutes; policy reports; publications in peer reviewed

journals Project lead Not applicable Type of activity Safety, immunogenicity, effectiveness, cost-effectiveness, impact

on young infant outcomes Location All countries Activity start 1/15/2013 Activity end 12/31/2018 Implementing organization

US Centers for Disease Control and Prevention; BMG Foundation


Source of funding US Government; Bill & Melinda Gates Foundation; GAVI


Activity Identification Policy development

Activity title National vaccine advisory committee, maternal immunization working group, phase II

Activity objective


Identify barriers to and opportunities for developing vaccines for pregnant women and make recommendations to overcome these barriers

Expected output Publication (recommendations report)

Project lead Dr. Jennifer Gordon/Dr. Karin Bok (NVPO leads); Dr. Richard Beigi/ Dr. Saad Omer (Chairs)

Type of activity Drafting recommendations for the Assistant Secretary for Health




National Vaccine Advisory Committee, National Vaccine Program Office, DHHS, US


Dr. Karin Bok

Source of funding Federal Budget


Activity Identification Feasibility and best practice

Activity title Evaluation of providing seasonal influenza vaccine to pregnant women in Armenia

Activity objective To evaluate the use of donated influenza vaccine doses in maternal immunization settings


In December 2014, Armenia received 60,000 doses of influenza through the Partnership for Influence Vaccine Introduction (PIVI). An evaluation will be conducted in 2015 to assess the use of the vaccine, the delivery model, and issues that can support sustainability of the program in Armenia.

Expected output Report to the Ministry of Health, information on the impact and sustainability of PIVI donations to maternal influenza immunization programs

Project lead Joe Bresee, Alan Hinman

Type of activity Evaluation project

Location Armenia



Task Force for Global Health, CDC (NCIRD, GID)


Sara Mirza

Source of funding PIVI



Activity title The use of the electyronic medical record to increase Tdap vaccination rates in pregnancy

Activity objective To determine antepartum Tdap vaccination uptake in pregnancy using an alert in our electronic medical record system


When the recommendation for Tdap changed to antepartum administration, we built an alert (BPA - best practice alert) in our electronic medical record (EPIC) to fire when the pregnant woman reached 30 weeks gestation. If she accepted the vaccine, the alert stopped. If she declined, the alert fired every visit so the provider remembered to readdress vaccination with the patient. We were able to increase our vaccination rate to 97% if the woman remained pregnant at 30 weeks when the BPA would fire.

Expected output Increase in Tdap vaccination rates

Project lead Jeanne S. Sheffield, MD

Type of activity Vaccination uptake




University of Texas Southwestern Medical Center


Jeanne S. Sheffield, MD

Source of funding No funding


Activity Identification Feasibility and best practice Activity title RSV Vaccine Project – protecting young infants through

maternal immunization Activity objective to protect infants through RSV maternal immunization Activity description

RSV

Expected output Project lead Type of activity Location United States, LIC TBD Activity start 11/19/2013 Activity end 11/1/2016 Implementing organization

PATH Vaccine Solutions




Activity Identification Feasibility and best practice Activity title Basic immunization (EPI) Activity objective To raise immunity in the Thai population against vaccine

preventable diseases Activity description

Provision of basic vaccines to target population groups through health service facilities in public and private sector, free of charge.Vaccines provided include: BCG, HBV, OPV, DTP-HB, JEV, MMR, dT, Influenza. Vaccines dT and Influenza are targeted for pregnant women. The program is ongoing since its start.

Expected output Annual report of Thai EPI program. Project lead Director, Bureau of General Communicable Diseases, Department

of Disease Control, Ministry of Public Health, Thailand Type of activity Vaccination coverage report. Location Thailand Activity start 1/1/1977 Activity end 12/31/2014 Implementing organization

Deprtment of Disease Control, Ministry of Public Health






Activity title EPI coverage survey

Activity objective To verify basic vaccination coverage in the Thai population


Community-based survey, using cluster sampling methodology, conducted every 1-5 years since the beginning of EPI program (1977). The last survey was conducted during January-March 2008

Expected output http://www.hiso.or.th/health_survey/DOC/vacsine.php

Project lead Director, Bureau of General Communicable Diseases, Department of Disease Control, Ministry of Public Health, Thailand

Type of activity Field survey of vaccination coverage.

Location Thailand



EPI program, Bureau of General Communicable Diseases, Department of Disease Control, Mnistry of Public Health, Thailand





Activity Identification Feasibility and best practice Activity title Planning for group B streptococcus vaccine development Activity objective To support an assessment of the feasibility and resource

requirements for developing a group B streptococcus vaccine Activity description

Group B Strep

Expected output Project lead Type of activity Location United States, South Africa Activity start 6/24/2014 Activity end 3/31/2015 Implementing organization

PATH Vaccine Solutions





Activity title A COMPREHENSIVE PRE-NATAL INTERVENTION TO INCREASE VACCINE COVERAGE

Activity objective Improve maternal immunization coverage


We developed and pilot tested a novel, innovative, evidence based, and comprehensive immunization intervention at the Practice, Provider, and Patient (P3) levels to meet the diverse and complex information needs of mothers.

Expected output Publication

Project lead Saad B. Omer

Type of activity vaccine effectiveness




Emory University


Xin-Xing Gu



Activity Identification Regulatory support

Activity title Enhanced survellance for adverse events following influenza vaccination in pregnant women

Activity objective Identify new or unusual vaccine safety signals in pregnant women


National collaborative efforts to prospectively review reports of advers events that occur in pregnant women who have been considered a priority for influenza vaccines beginning 2014-2015 influenza season

Expected output Weekly reports during nationwide mass immunization campaign (http://adr.fda.gov.tw). Seaonsal summary available in April

Project lead Wan-Ting Huang MD and Wei-I Huang MS

Type of activity Vaccine safety initiatives

Location Taiwan

Activity start 1/10/2014 Activity end 12:00:00 AM


Taiwan Centers for Disease Control, Taiwan Food and Drug Administration, and Taiwan Drug Relief Foundation


Wan-Ting Huang MD

Source of funding Taiwan Centers for Disease Control and Taiwan Food and Drug Administration



Activity title US FDA draft guidance on pregnancy and lactation labeling for human prescription drug and biological products

Activity objective To assist sponsors of license applications to comply with the new content and format requirements in the Pregnancy, Lactation, and Females and Males of Reproductive Potential subsections of US FDA labeling for human prescription drug and biological products.


The FDA recently published the final Pregnancy and Lactation Labeling Rule, along with draft guidance. The guidance (www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm425398.pdf) is intended to assist applicants in complying with the new content and format requirements in the Pregnancy, Lactation, and Females and Males of Reproductive Potential subsections of US FDA labeling for human prescription drug and biological products.

Expected output

Project lead

Type of activity Regulatory support




US FDA


Source of funding



Activity title Report back of WHO consultation on labelling of inactivated influenza vaccines for pregnant women

Activity objective Facilitate regulatory approval of surveillance data to support a labelling indication for use of inactivated influenza vaccines in pregnant women.


Presentation and discussion with DCVRN members and regional observers

Expected output DCVRN meeting report to include Points to Consider on influenza vaccine use in pregnant women

Project lead JA Southern : Chair of Developing Country Vaccine Regulators' Network

Type of activity Analysis of published evidence supporting use of influenza vaccines in pregnant women

Location Brazil,China,Cuba,India,Indonesia,Iran (Islamic Republic of),Republic of Korea,South Africa,Thailand



DCVRN


James Southern




Activity title WHO Activities to facilitate RSV, vaccine development, licensure, prequalification and use with a focus on low and middle income countries

Activity objective To advance global standards and norms for RSV vaccine development, WHO prequalification and ultimately use of RSV vaccines to protect kids in low and middle income countries


RSV

Expected output

Project lead Vasee Moorthy

Type of activity

Location Switzerland





Vasee Moorthy



Activity Identification Training and tools

Activity title Effect of nutrition, immunity, and vaccines on pediatric enteric infections

Activity objective Train clinical investigators


Identify effective interventions to optimize a population's natural and vaccine-acquired immunity to diarrhea-inducing enteric viruses like rotavirus (RV) and norovirus (NoV) and thereby protect children from diarrhea.

Expected output Publications

Project lead Juan S. Leon

Type of activity Analysis of disease trends




Emory University


Rodolfo M. Alarcon



Activity Identification Training and tools Activity title Increasing immunization rates in Ob-Gyn practices Activity objective Activity description

The American College of Obstetricians and Gynecologists (ACOG) is strongly committed to maternal immunization. Below is a summary of ACOG’s activities related to Maternal Immunization.In 2005 ACOG convened a task force to strengthen the role of ob-gyns in providing immunizations to women. In 2010, partly in response to the H1N1 pandemic, ACOG turned this task force into a standing work group made up of many immunization and infectious disease experts. The Immunization Expert Work Group guides ACOG’s immunization activities and many of its members serve on several national advisory groups. These include a voting member and several liaisons to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP), National Vaccine Advisory Committee (NVAC) Maternal Immunization work group, and the Vaccines and Medications in Pregnancy Surveillance System (VAMPSS). ACOG has executed several surveys to assess ob-gyns knowledge, attitudes, beliefs and practices surrounding immunizations including maternal immunizations. ACOG also has several committee opinions addressing maternal immunization. Committee Opinions serve as official guidance from ACOG. Since 2011 ACOG has conducted immunization trainings in over 70 ob-gyn practices in the midwest and Texas to help educate ob-gyns and give them the tools needed to increase their immunization programs. These trainings included evaluation via pre/post surveys assessing immunization practices and identifying barriers to maternal immunization. In addition to the surveillance, guidelines, and trainings, ACOG has developed a robust collection of maternal immunization resources for providers and patients. These resources include:• A website dedicated to providing up to date immunization information to women and providers: www.immunizationforwomen.org• Frequently Asked Questions for patients addressing maternal immunization topics such as Influenza, Tdap, and Vaccine Safety during Pregnancy• Frequently Asked Questions for providers addressing these same topics• Business Practices resources addressing coding and reimbursement• Several webinars for providers which can be accessed from the Immunization for Women website addressing Influenza, Tdap, and general immunization topics. • Several tool kits for providers addressing maternal immunization topics include Influenza and Tdap.

Expected output Project lead Type of activity





The American College of Obstetricians and Gynecologists (ACOG)


Sarah Patterson Carroll

Source of funding These projects have been funded through several cooperative agreements from the Centers for Disease Control and Prevention and several unristricted educational grants from Merck.


Activity Identification Training and tools Activity title ACOG expert workgroup on immunization Activity objective Helps ACOG produce educational materials on maternal

immunization and also attempts to measure practice changes Activity description

Website www.immunizationforwomen.orgMultiple webinars for specific vaccinesTool kits for flu, tdap and HPVCommittee opinions on above vaccines

Expected output www.iimunizationforwomen.org Project lead Debra Hawks and Sarah Patterson Type of activity Educational materials Location United States of America Activity start Activity end Implementing organization

American College of Obstetricians and Gynegologists


Sarah Patterson

Source of funding ACOG, CDC, ASTHO


Activity Identification Training and tools

Activity title Maternal health influenza costing tool

Activity objective To develop a costing tool for introduction of influenza vaccine for pregnant women in low and lower-middle income countries


Developing a costing tool for program managers to estimate the resource requirements of introduction influenza vaccine for pregnant women

Expected output Cost tool and user manual

Project lead Raymond Hutubessy

Type of activity cost analysis




Levin and Morgan Health


Ann Levin



Activity Identification Ethics and liability issues Activity title Scientific workshop to discuss different vaccination

strategies for Respiratory Syncytial Virus (RSV) Activity objective to organize workshop to provide a platform for discussion on the

potential risks and benefits of novel vaccination strategies for respiratory syncytial virus (RSV) and to define the criteria for advancing vaccine studies in different populations


RSV

Expected output Project lead Type of activity Location United Kingdom Activity start 11/4/2014 Activity end 3/30/2015 Implementing organization

University of Oxford




Activity Identification Global collaboration

Activity title Partnership for influenza vaccine introduction in low and lower middle-income countries

Activity objective To fund a partnership for influenza vaccine introduction in low and lower middle-income countries


Influenza

Expected output

Project lead Alan Hinman

Type of activity

Location Lao People's Democratic Republic, Nicaragua



The Task Force for Global Health, Inc.


Alan Hinman



Activity Identification Global collaboration Activity title Fifth ESWI Influenza Conference Activity objective To promote international and multidisciplinary collaboration to

develop new intervention strategies to better protect pregnant women and their unborn children against both seasonal and pandemic influenza


Influenza

Expected output Project lead Type of activity Location Latvia Activity start 4/4/2014 Activity end 3/31/2015 Implementing organization

ESWI




Activity Identification Global collaboration Activity title Clinical Research in pregnant women: knowledge, gaps

and opportunites Activity objective knowledge, gaps and opportunites for research duing pregnancy

with emphasis to LMIC Activity description

Consultative conference

Expected output Meeting Report: special issue of Vaccine devoted to Maternal

Immunization Project lead Mirjana Nesin Type of activity analysis of vaccine effectiveness Location All countries Activity start 9/28/2014 Activity end 9/29/2014 Implementing organization

NIH/BMGF


Mirjana Nesin

Source of funding NIH/BMGF


Documents

Maternal Immunization Research and Implementation Portfolio · Determine the barriers to effective tetanus toxoid implementation as a maternal vaccine, to identify necessary actions