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Prevention of Meningococcal Disease
Marco Aurélio P. Sáfadi, MD, PhDFCM da Santa Casa de São Paulo
Neisseria meningitidis
• Polysaccharide capsule (12 serogroups) A, B, C, Y, X and W….
• Genetic characterization (DNA sequencing of 7 housekeeping genes - MLST)
• Whole genome phylogenetic analyses
Lucidarme J et al. J Infect, 2015
Meningococcal Disease
Clinical syndromes
• Bacteriemia (37.5%) -Meningococcemia
• Meningitis (50%)• Pneumonia (9%)• Conjunctivitis arthritis,
pericarditis, urethritis
D. Pace, A.J. Pollard / Vaccine 30S (2012) B3–9
IMD Can Result in Permanent, Long-term SequelaeOn average, 10%–20% of surviving patients
have long-term sequelae1Typical sites of IMD sequelae1-5
1. World Health Organization. Meningococcal meningitis. Fact sheet No. 141. Updated November 2015. http://www.who.int/mediacentre/factsheets/fs141/en/. Accessed August 26, 2017. 2. BettingerJA, et al. Pediatr Infect Dis J. 2013;32:e20-e25. 3. Viner R, et al. Lancet Neurol. 2012;11:774-783. 4. Borg J, et al. Pediatrics. 2009;123:e502-e509. 5. Brandtzaeg P. In: Frosch M, et al, eds. Handbook of Meningococcal Disease: Infection Biology, Vaccination, Clinical Management. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA; 2006:427-479.
Typical Symptoms of IMD Appear Later in Older Children and Adolescents, Delaying Medical Care and Increasing the Risk of Long-
term Effects of IMD
Thompson MJ, et al. Lancet. 2006;367:397-403.
Timely GP/hospital admission is critical for successful treatment of IMD.
810
15
19
13 14
2022
0
5
10
15
20
25
Meningococal disease: risk factors1–3
• Infants / adolescents• Terminal complement /
properdin deficiency• Anatomic or functional
asplenia• Lab workers• HIV+ / MSM• Genetic polymorphism
• Clonal complex• Bacterial load• Circulating endotoxins
• Household crowding• Exposure to tobacco smoke• Low socio-economic status• Urban residence
Host Pathogen
Environment
Most cases (>90%) of meningococcal disease occur in previously healthy persons without identified risk factors2
MSM were several times more likely to contract invasive meningococcal disease than other males aged 18–64 years
Kratz MM, et al. Emerg Infect Dis 2015;21:1379–86
Children and adults with HIV have increased (up to 26.5-fold) risk of meningococcal disease
Simmons R, et al. BMC Med 2015;13:297
There is a 1,000-fold increased risk of meningococcal disease (caused by unusual meningococcal strains) in patients with complement deficiency
Rosain J, et al. J Infect Dis 2017:215:1131–8
Eculizumab use has been primarily associated with an increased risk (up to 10,000-fold higher) of meningococcal infections
Benamu E, et al. Curr Opin Infect Dis 2016;29:319–29
1. Rosenstein N et al. N Eng J Med 2001;344:1378–88. 2. Kaplan SL et al. Pediatrics 2006;118:e979–84 3. MMWR. Prevention and Control of Meningococcal Disease. Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/rr4907a1.htm (accessed May 2018)
Carriage and transmission • Pharyngeal carriage is a prerequisite for invasive meningococcal
disease.• Asymptomatic carriage (may last a long time) -nasopharynx (< 1% - 30%)• N. meningitidis is predominately carried by teenagers/young adults.
Prevalence (%)
Age
0
20
40
60
0 20 40 60 80 100
Fitted dataRange of 95% CI
Christensen H et al. Lancet Infect Dis. 2010;10:853.
Worldwide Available Polysaccharide Conjugate Meningococcal Vaccines
Polysaccharide Conjugate Vaccines Carrier Protein46-53
Menjugate MenC CRM197Meningitec MenC CRM197NeisVac-C MenC TTMenitorix MenC-Hib TTMenAfriVac MenA TTMenactra MenACYW DTMenveo MenACYW CRM197Nimenrix™ MenACYW TT
New multivalent ACWY-TT and ACWYX vaccines are being developed
Menjugate® [PI]. Novartis Vaccines; 2013; 47Meningitec® [PI]. Pfizer; 2011; 48NeisVac-C® [PI]. GlaxoSmithKline Inc; 2010; 49Menitorix® [PI]. GlaxoSmithKline Australia; 2013; 50MenAfriVac® [PI]. Serum Institute of India Ltd; 51Menactra [PI]. Sanofi pasteur; 2013; 52Menveo [PI]. Novartis Vaccines; 2013; 53Nimenrix® [PI]. GlaxoSmithKline UK; 2013; 54Meningo A+C [Public assessment report]. Sanofi Pasteur; 2013; 55Mencevax® [PI]. GlaxoSmithKline Australia; 2010; 56Menomune® [PI]. Sanofi pasteur; 2012.
Meningococcal Conjugate Vaccines Represent a Significant Advance Compared With Existing Plain Polysaccharide Vaccines
Polysaccharide vaccine• Antibody response of short
duration• No memory B-cell production
Polysaccharide
B cell
Antibody production
Plasma cell
Conjugate vaccine• Antibody response of long
duration• T cells stimulate B cells to
produce antibodies• Memory B cells produced
Carrier protein
B cell
BCR
T-cell help
Polysaccharide-specific plasma cell
Antibody production
Polysaccharide-specific memory B cell
43Pollard AJ, et al. Nat Rev Immunol. 2009;9(3):213.
10
Outbreaks caused by MenC.High carriage rates of MenC in both refineries. No impact of vaccination on carriage rates
%
Ministry of Health replace the polysaccharide vaccine with the MenC conjugate vaccine for controlling MenC outbreaks
Update on safety and immunogenicity (reduced schedule,
concomitant administration and persistence data) of meningococcal
conjugate vaccines
0102030405060708090
100
SBA
titer
s≥
1:8
(%)
< 6 m
12%
5-11 m
16%
12-23 m
26%
24-35 m
23%
36-47 m
33%
Antibody Persistence 6 years After Vaccination with MenC Conjugate
48-59 m 60-83 m
26%
48%
Perrett K et al. CID, 2010
• Persistence of immunity is dependent on age at priming• These data emphasizes the importance of the herd immunity effect and
provide the first evidence supporting the introduction of a booster dose for cohorts of children immunized before school age.
Age (in months) at priming vaccination
Antibody persistence 5 years after primary vaccination with MenACWY-CRM in infants, and booster response across all serogroups2,3
1. Klein NP et al. Pediatr Infect Dis J 2012;31:64–71; 2. Baxter R et al. Hum Vaccin Immunother 2016;12:1300–1310;3. Klein NP et al. Open Forum Infect Dis 2014;1(Suppl 1):S319. Adapted from references 1–3
1 month post-dose 4(dose 4 at 12 months of age)1n=84–8628 months post-dose 4 (at 40 months of age)2
48 months post-dose 4 (at 60 months of age)2,3
Booster dose at 48 months post-dose 4(at 60 months of age)3n=103–115
*Blood drawn at 13 months of age (1 month post–dose 4), 40 months of age (28 months post–dose 4), 60 months of age (48 months post–dose 4) and 61 months of age (1 month post–booster at 60 months of age).
14
n=120–122
Time points assessed*:
**P
Real-World Impact data on Meningococcal Vaccines Programmes implemented in
Europe, Africa, North and Latin America
18
Direct and indiret protection with conjugated vaccines
Preventing the acquisition of carriage is crucial to optimize the impact of programs with conjugated vaccines
Vetter, Baxter, Sáfadi et al. ERV, 2016
19
MenC immunization programmes have reduced the burden of meningococcal C disease in Europe1–3
1. Trotter CL et al. FEMS Microbiol Rev. 2007;31:101–7; 2. Safadi M, McIntosh E. Expert Rev Vaccines 2011;10:1717–30; 3. de Greeff S et al . Pediatr Infect Dis J. 2006;25:79–80
Single dose of MenC-TT vaccine at 14 months + catch-up from 1‒18 years in Netherlands, 2002
Routine immunization programmes, including catch-up campaigns in children and adolescents, have been successful in reducing MenC disease incidence through
direct and indirect protection
54.5
43.5
32.5
21.5
10.5
0 Belgium(2002)
Iceland(2002)
Ireland(2000)
Netherlands(2000)
Spain(2000)
UK(1999)
Country (year of vaccine introduction)
Inci
denc
e
Meningococcal disease epidemiology in France, 2006-2015
Low MenC vaccination coverage in older age groups (32% in 10-14 y, 23% in 15-19 y and 7% in 20-24 y).
Incidence rates of MD, by serogroup. France, 2006-2015 Decreasing incidence of IMD cases in France from 2006 to 2015 (mainly related to the decrease in MenB cases).
Chatelet et al. Journal of Infection (2017) 74, 564e574
MenC Incidence rates. France, 2006-2015
21
• Incidence of suspected meningitis cases declined by 57% (95% CI 55–59) in vaccinated compared with unvaccinated populations.
• In fully vaccinated populations, the incidence of confirmed group A disease was reduced by more than 99%.
• The IRR for non-A serogroups was higher after completion of MenAfriVac campaigns (IRR 2·76, 95% CI 1·21–6·30).
Impact of MenA-TT vaccination in the “African belt”.
Trotter C et al. Lancet Infect Dis, May 2017
• Between 2011- 2015 > 217 million (1 – 23 y) vaccinated in 19 countries from the “meningitis belt” with MenA-TT
Emergence of MenC and MenW disease in Africa.
• By June 2015, 8,500 suspected cases of MD in Niger, including 573 deaths. Most of the cases were MenC, belonging from a newly lineage ST-10217.
• Nigeria: Dec/2016 - May/2017: 14,473 cases. 80% of tested cases were serogroup C.
• The world’s largest reported serogroup C epidemic
http://www.who.int/csr/don/23-july-2015-niger/en/ http://www.meningvax.org/files/BulletinMeningite. http://www.who.int/wer March, 2017 http://www.ncdc.gov.ng/themes/common/files/sitreps/bf8ebe6d8a8187aa9ddf1b39aecda3ae.pdfMustapha M & Harrison L. HVI, 2018
• Outbreaks of MenW cc-11 in Burkina Faso from 2012 and Togo and Ghana in 2016
• Reactive vaccinations in 2016 with polysaccharide ACW, AC and ACW and MenC conjugate vaccines
Distribution of MD cases in the meningitis belt, 2006 - 2017
http://www.who.int/csr/don/23-july-2015-niger/en/http://www.meningvax.org/files/BulletinMeningitehttp://www.who.int/werhttp://www.ncdc.gov.ng/themes/common/files/sitreps/bf8ebe6d8a8187aa9ddf1b39aecda3ae.pdf
Examples of Meningococcal conjugate vaccination
programmes without catch-up campaigns:
Brazil and Chile
Brazil started vaccination with MenC Vaccine for all children < 2 years of age on late 2010.
• Infant immunization (3 and 5 months) with booster dose at 12 months.
• Children between 12 and 23 months: 1 dose• No catch up campaign in older age groups
80%
13%5%1%
Incidence rates before and after Men C vaccination. Brazil, 2008-2015
0
2
4
6
8
10
12
14
16
< 1 a. 1-2 a 2-3 a 3-4 a 4-5 a 5-9 a 10-14 a 15-19 a 20-30 a 30-40 a 40-50 a 50-60 a > 60 a.
2008-2010 (pre-vaccine)20112012201320142015
Cases/100,000
Safadi M, et al. JPIDS. 2014;3:91-93SINAN, MS 2015.
Early impact on incidence rates of meningococcal disease observed only in the age groups targeted for vaccination.
Serogroup Distribution of MD, by age group. Brazil, 2017
SIREVA. IAL, 2017
28Macedo L et al. HUMAN VACCINES & IMMUNOTHERAPEUTICS 2018,
VaccinationVaccination
Impact of MenC conjugate vaccination programs with and without catch-up campaigns in adolescents: Bahia, Brazil
Children < 5 years of age + catch-up campaign for individuals 10–24 years of age
Only Children < 5 years of age
In Salvador, compared to the pre-vaccine period, a virtual disappearance of MenC disease was observed. However, in the state of Bahia (excluding the city of Salvador), no herd protection could be observed, with significant impact only among vaccine-eligible children within 5 years of introduction of the MCC vaccination program
Booster doses in adolescents 9-13 years with MenC conjugate vaccine.
Decision for 2017 with MenC conjugate vaccine in Brazil:
Incidence rates and CFR of Meningococcal Disease in Chile. 1990-2015
Increased incidence of MD in 2012 (from 0.4 to 0.8), associated with emergence of serogroup W (3 cases in 2010, 20 in 2011 and 60 in 2012).
http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf
CFR
(%)
Inci
denc
e ra
tes
(per
100
,000
hab
)
Reactive MenW Immunization action in Chile
http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf
• An immunization campaign started in 2012 with the tetravalent conjugate vaccine (Men ACWY), initially targeting children aged 9 months to < 5 years.
• 9 m to < 2 y: 2 doses (MenACWY-DT) and > 2 y: 1 dose (MenACWY-CRM).
• Approximately 1 million children vaccinated (Coverage >95%).
• From 2014: 1 dose (MenACWY-TT) in toddlers at 12 months.
Impact of the MenACWY immunisation campaign in Chile, 2012-2017
Inci
denc
e ra
tes
(cas
es/1
000)
ISP, Chile
82% reduction
• Reduction of 82% in the incidence rates of MD in children aged 1- 5 years• No significant impact on incidence rates of other unvaccinated age groups
Age (years)http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf. 2017http://www.ispch.cl/sites/default/files/Informe%20Neisseria%20meningitidis%20%20SE%201-5%202018%20v%203.pdf
0
5
10
15
20
< 1Y 1-5 Y 6y - 9 y 10y - 19y 20y - 59y > 60y
201220132014201520162017
Pre-vaccine
Post-vaccine
http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf
Number of cases of serogroup W cases. Chile, 2010 - 2017
0
20
40
60
80
100
120
2010 2011 2012 2013 2014 2015 2016 2017
serogroup W cases
W
ACWY Vaccination
http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf. 2017http://www.ispch.cl/sites/default/files/Informe%20Neisseria%20meningitidis%20%20SE%201-5%202018%20v%203.pdf
http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf
Meningococcal Disease in US.
• In 2016, 372 cases of MD reported (0.12/100,000). Declining incidence rates.
• 49 deaths (CFR 13%)
CDC, 2018 (http://www.cdc.gov/meningococcal/surveillance/)
• Highest rates in infants, followed by a second peak in adolescence (16-23 y) and elderly.
• Serogroup B causes ~ 60% of cases in children < 5 years old. Serogroups C, Y, or W cause 73% of the cases among persons > 11 years old.
37
Age Group Primary BoosterIndividuals 11–21 years
11–12 years 1 dose Given if 1st dose before 16th birthday
5 years post primary; 13–18 years (not vaccinated) 1 dose
19–21 year (not vaccinated by 16) 1 dose as catch-up
High risk individuals
2–18 months at high risk 4 doses at2, 4, 6, 12–15 months
2 mos–6 years: 3 years post primary; Every 5 years thereafter
≥7 years: 5 years post primary; Every 5 years thereafter
9–23 months at high risk 2 doses 12 weeks apart
2–55 years at high risk 2 doses 12 weeks apart
2–55 years students, travelers, etc 1 dose
≥56 years MPSV4 (primary recommendation)
Every 5 years with MenACWY if the person remains at risk
Recommendation of meningococcal vaccination in USA (ACIP)
MMWR, 2016
Men ACWY conjugate vaccine is routinely recommended for all adolescents and high risk individuals.
Vaccine effectiveness of MenACWY-D: Case-Control Study in Adolescents*
Cases (N=183)*Controls (N=199) VE (95% CI)
Vaccinated < 1 year 79% (54%-93%)
Vaccinated 1< 3 years 69% (44%-83%)
Vaccinated ≥ 3-8 years 61% (25%-79%)
McNeil J et al. PEDIATRICS Volume 139 , number 2 , February 2017
• Vaccine effectiveness was 77% and 51% for serogroups C and Y, respectively. Vaccine effectiveness against serogroup W could not be calculated due to the low incidence.
• Effectiveness waned 3 to
39
The “South-American” serogroup W evolution.
An expanding South American/UK MenW strain was distinct from the ‘Hajj outbreak’ strain.Jay Lucidarme et al. Journal of Infection 2015
These data also demonstrate the co-circulation of W ST-11 strains in South America, UK and other regions that are phylogenetically and antigenically distinct from the Hajj cloneMustapha M et al. Ebio Medicine, 2015
The Jamboree-associated cluster formed part of a novelstrain, the proposed ‘2013-strain’, which emerged in the UK in 2013.Lucidarme J et al. Euro Surveill. 2016
40
Emergence of serogroup W in UK• In the light of the rapidly increasing W (cc11) disease from 2009/10
to 2014/15, ACWY conjugate vaccine was introduced in late 2015 for 13-18 years teenagers and university freshers and is intended to induce herd protection.
Campbell H et al, Euro Surveill. 2015; Campbell H et al, Euro Surveill. 2016
• A quarter of cases occurred in children aged
41
No cases in adolescents vaccinated with MenACWY.Early estimated vaccine effectiveness was 100% (−47% - 100%)
Observed and projected cases of W, Y, and B MD in England among persons who left school
• MenACWY coverage of 36,6% among persons who left school.
• During the first 12 months of the MenACWY vaccination program for teenagers, a 69% decrease (18%–88%) was observed.
Campbell H et al. Emerg Infect Dis. 2017 Jul
Meningococcal Disease, Australia 2002-2017.
• There is currently an outbreak of Meningococcal W (MenW) in Central Australia.
• In response, six states have started a meningococcal ACWY vaccination program for individuals in affected communities. The programs target adolescents aged 15-19 years, with NSW targeting 17-18 year olds..
http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-meningococcal-W.htm
43
Serogroup W disease in Netherlands
Knol M et al. Lancet Public Health 2017; 2: e473–82
• In the Netherlands, the incidence of meningococcal serogroup W disease increased substantially in 2015–16 compared with 2014–15, with an incidence rate ratio of 5·2 (95% CI 2·0−13·5) and 11% case fatality
Cases of MenW disease caused by the South American MenW:cc11 strain sublineage
• The outbreak started mainly among people aged 65 years and older, with an increase among 10−19 year olds in 2016
• MenC was replaced by MenACWY in adolescents to prevent further serogroup W cases and deaths
1. Tsang RSW, et al. Can Commun Dis Rep 2017; 43:144–9. 2. Tsang RSW, et al. Int J Infect Dis 2018;69:55–62
Emergence of MenW in Canada
• Increase of MenW in Canada, associated with emergence of ST-11 CC.
• The % of Men W isolates varied from 2.7% in 2012 to18.8% in 20161
• WGS: evidence of presence “Hajj-related” and non-Hajj MenW ST-11 CC (related to “South American sub-lineage strains”)2
Canada
Prevalence of carriage by serogroup
Despite 71% MenACWY vaccine coverage, carriage of group W increased substantially.
Majority belongs to MenW:ST-11 cloneOldfield N et al. EID, 2017
0
2
4
6
8
10
12
sep/15 nov/15 mar/16
Carri
age
preva
lence
(%)
NG B Y W Non BWY
cross-sectional meningococcal carriage study in first-year UK university students
Meningococcus B capsule is a self antigen, poorly immunogenic and cannot be used for vaccination
1Häyrinen J, et al. J Infect Dis. 1995;171:1481-1490; 2Finne J, et al. J Immunol. 1987;138:4402-4407; 3Bruge J, et al. Vaccine. 2004;22:1087-1096;
• Structurally identical polysialic acid units in fetal neural tissue
• Poorly immunogenic1,2• No functional activity of
vaccine-induced AB3
The polysaccharide capsule?
Poorly immunogenic1
A single subcapsular protein component?
Susceptible to antigenic variability2,3
Multiple subcapsular components?
Enables broad coverage across a number of strains4
A Multicomponent Approach to MenB Vaccination
1. Häyrinen J, et al. J Infect Dis. 1995;171:1481-1490; 2. Sadarangani M, et al. Lancet Infect Dis. 2010;10:112-124; 3. Tan LK, et al. N Engl J Med. 2010;362:1511-1520; 4. Donnelly J, et al. Proc Natl Acad Sci U S A. 2010;107:19490-19495.
Neisseria meningitidis
Factor H (fH) binding protein (fHBP) vaccine - Pfizer• Virulence factor
• Binds fH→ down regulates alternative complement pathway
• 3 variant groups:
• Variant 1 (family B),
• Variants 2 and 3 (family A).
• Two lipidated LP2086 variants in Pfizer vaccine were selected (one from each subfamily)
• 2 doses: 0 – 6 months or 3 doses: 0, 1-2 and 6 months (10 – 25 years of age)
MATS Concept
Are any of the 4CMenB components in the circulating strains: (i) expressed to a sufficient degree, and (ii) similar enough to the antigens in the vaccine such that the antibodies
generated by 4CMenB will kill the bacteria?
MATS can determine the minimum amount of recognizable antigen needed to result in bacterial killing, for each of the four components*
1. fHbp, NHBA and NadA assessments use ELISA PHENOTYPIC2. PorA assessment uses PCR sequencing GENOTYPIC
*individually
4CMenB Vaccine - GSK
4CMenB Vaccine Licensed Immunization SchedulesEuropean Union
BEXSERO [summary of product characteristics].
3 Doses2–5 months
6–11 months
12–23 months
2–10 years
11+ years
≥1 month 1 Dose age 12–15 mo*
2 Doses
≥2 months
≥1 month
1 Dose in the 2nd year of life≥2 mo post–primary series
1 Dose 12–23 mo post–primary series
Need not established
Age Group Primary ImmunizationInterval Between Primary Doses Booster
*In case of delay, the booster should not be given later than 24 months.
Canada (2006–2009): Bettinger JA, et al. Vaccine. 2013;32:124-130; United States (2000–2008, data downweighted with Oregon outbreak strains): Kim E, et al. Presented at: 18th IPNC. September 9-14, 2012. Würzburg, Germany. Poster P270; Brazil (2010): Lemos AP, et al. Presented at: 18th IPNC. September 9-14, 2012. Würzburg, Germany. Poster P272; Norway, United Kingdom, Germany, France and Italy (July 2007–June 2008), Spain (2008–2010): Vogel U, et al. Lancet Infect Dis. 2013;13:416-425; Greece (2008–2010): Data on file, Novartis Vaccines and Diagnostics; Ireland (2009–2013): Data on file, Novartis Vaccines and Diagnostics; Australia (2007–2011): Tozer SJ, et al. Poster presented at: 27th ICP; August 24-29, 2013. Melbourne, Australia.
Estimated Potential MenB Strain Coverage for specific countries based on MATS
85%
73% 82%85%
87%85%82%
87%
85%
73%
69%88%
74%
76%
66%
91%
81%
68%
Read R et al. ESPID 2013
Impact of 4CMenB on carriage.
Outbreak of serogroup B disease in Saguenay-Lac-Saint-Jean, Canada.
• Serogroup B (ST-269) clone emerged in Quebec, Canada.
• Incidence rate of 3.4/100,000 from 2006 to 2013.
• After vaccination of population (2 m-20 years) with 4CMenB decreases were, respectively 92% and 67%, in age-group ≤20 years and in those > 20 years
De Wals et al. CID, 2017
Meningococcal disease on US college campuses, 2013–17
1. http://www.nmaus.org/wp-content/uploads/2017/12/NMA-College-Outbreak-Map-December-11-2017.pdf2. MMWR Morb Mortal Wkly Rep. 2015
UK Immunization Recommendations for Meningococcal Vaccines
AGE Immunisation (Vaccine Given)
2 months • MenB
4 months • MenB
Between 12 - 13 months
• Hib/MenC (combined as one injection); plus: • MenB
13-18 years • Men ACWY - given to 17-18 year olds and first time students up to 25 years.
http://www.nhs.uk/conditions/vaccinations/pages/vaccination-schedule-age-checklist.aspx
MenACWY – recommended for travelers to Mecca for religious festivals of Hajj or Umrah
Impact: Comparing with the pre-vaccine period, a 50% reduction in MenB incidence rates was observed in the cohorts eligible for vaccination (p=0·0001).
Lancet, online 27 October 2016
Effectiveness:• One dose of the vaccine: 22% (95% CI –105 to 67,1).• Two doses of the vaccine: 82,9% (95% CI 24,1–95,2).• At least one dose of the vaccine: 64% (95% CI 8,9–84).
UK introduced the MenB vaccination in September 2015 for infants at two and four months of age, with a booster dose at 12-13 months (high coverage)
58
Age distribution of group W cases, by academic year, England, 2011 – 2016.
Cases and incidence rates increased in every age group except persons 15–19 years of age (31% reduction) and infants
• Samples of infants vaccinated with Bexsero presented hSBA > 1/32 against W cc11 meningococcal strains.
60
Lancet 2017
Booster doses in adolescents with conjugate vaccines.
Use of the protein-based Men B vaccines
Considerations for the future with meningococcal vaccines:
Slide Number 1Neisseria meningitidisMeningococcal DiseaseIMD Can Result in Permanent, Long-term SequelaeTypical Symptoms of IMD Appear Later in Older Children and Adolescents, Delaying Medical Care and Increasing the Risk of Long-term Effects of IMDMeningococal disease: risk factors1–3Carriage and transmission Worldwide Available Polysaccharide Conjugate Meningococcal Vaccines�Meningococcal Conjugate Vaccines Represent a Significant Advance Compared With Existing Plain Polysaccharide VaccinesOutbreaks caused by MenC.�High carriage rates of MenC in both refineries. �No impact of vaccination on carriage ratesUpdate on safety and immunogenicity (reduced schedule, concomitant administration and persistence data) of meningococcal conjugate vaccinesSlide Number 13Antibody persistence 5 years after primary vaccination with MenACWY-CRM in infants, and booster response across all serogroups2,3Antibody persistence after MenACWY-CRM or MenACWY-DT up to 5 years after primary vaccination in adolescents aged 11–18 yearsSlide Number 17Direct and indiret protection with conjugated vaccinesMenC immunization programmes have reduced the burden of meningococcal C disease in Europe1–3Meningococcal disease epidemiology in France, 2006-2015Slide Number 21Emergence of MenC and MenW disease in Africa.Examples of Meningococcal conjugate vaccination programmes without catch-up campaigns:�Brazil and ChileSlide Number 24Incidence rates before and after Men C vaccination. Brazil, 2008-2015Serogroup Distribution of MD, by age group. Brazil, 2017Slide Number 28Slide Number 29Slide Number 30Slide Number 31Impact of the MenACWY immunisation campaign in Chile, 2012-2017Number of cases of serogroup W cases. Chile, 2010 - 2017Meningococcal Disease in US. Recommendation of meningococcal vaccination in USA (ACIP)Vaccine effectiveness of MenACWY-D: Case-Control Study in Adolescents*The “South-American” serogroup W evolution. Emergence of serogroup W in UKNo cases in adolescents vaccinated with MenACWY.�Early estimated vaccine effectiveness was 100% (−47% - 100%)Meningococcal Disease, Australia 2002-2017.Slide Number 43Emergence of MenW in CanadaPrevalence of carriage by serogroupMeningococcus B capsule is a self antigen, poorly immunogenic and cannot be used for vaccinationA Multicomponent Approach to �MenB VaccinationFactor H (fH) binding protein (fHBP) vaccine - PfizerMATS Concept4CMenB Vaccine Licensed Immunization Schedules�European UnionEstimated Potential MenB Strain Coverage for specific countries based on MATS Slide Number 52Slide Number 53Outbreak of serogroup B disease in Saguenay-Lac-Saint-Jean, Canada. Meningococcal disease on US college campuses, 2013–17UK Immunization Recommendations for Meningococcal Vaccines�Slide Number 57Age distribution of group W cases, by academic year, England, 2011 – 2016.Slide Number 59Slide Number 60Slide Number 61