Current limitations on the use of vaccination against avian influenza

Ian BrownDirector of EU/OIE/FAO International Reference Laboratory for Avian Influenza, Newcastle Disease and Swine InfluenzaAnimal and Plant Health Agency-Weybridge

AVI AFRICA 2018, SAPA Conference & Exhibition12 - 14 June 2018 Gauteng

2

HPAI outbreaks 2017

3

HPAI outbreaks poultry 2018

HPAI H5N1 ancestral virusGoose/Guangdong/96

Multiple waves new strains – virus constantly evolving (Goose/Guangdong lineage)

• Antigenetic change – HA• Accumulated changes

• Genotypic variation• Genetic reassortment

• 1997- H5N1 multiple clades (0, 1, 2, 7)• 2.2 spread to Europe/Africa • 2.1 spread to Indonesia

• 2009 – H5N1, selection of clades with greater fitness for birds• ie clade 2.3.2.1 spread to West Africa

• 2013 – H5N2, H5N8, H5N6• ie clade 2.3.4.4 spread to ‘African continent’

Text in footer 5

APHA 2017 6

2.3.4.4

HA Clade of H5 HPAI viruses isolated in October 2014 – January 2018

2.3.4.4

2.3.4.4

2.3.4.4

2.3.4.42.3.2.1c

2.3.2.1c

2.2.1

2.3.2.1c

2.3.2.1c, 2.1.3.2a

2.3.2.1a2.3.2.1c

2.3.2.1c

2.3.4.4

2.3.4.4

Occurrence of HPAI in South Africa 2011-18

• 2011-2013 H5N2- ‘locally derived’

• 2017 H5N8 – transcontinental spread• 2018 H5N8 – transcontinental spread

• 2019-???

Text in footer 8

Future perspectives for global poultry production

• Understanding pathways for introduction• Ongoing threat from infected nearby countries- H5 viruses• Endemic strains ie H9N2, H6N2• Virus variability; correlates for infection risk

• Poultry industry associated spread• Live birds, commodities, fomite

• Human behaviour: migration, societal factors• Global Food security and zoonotic risk• Trade impacts and risks• Regional contingency and preparedness

• Early detection and control measures• Vaccination

• Solutions at global scale for better interventions• Better veterinary vaccines

Desired results of vaccination against AI

• freedom from disease• no effect on production or other serious expense• no trade embargoes• Eradication if enzootic infection

APHA 2017 10

Avian influenza vaccination

Current vaccines can result in:• Protection against clinical signs• Decrease bird susceptibility to infection• Reduction in virus excretion• Reduction in transmission (birds and humans)BUT………….

AI vaccination - caution

• AI virus may infect and replicate in vaccinated birds without clinical signs

• As a corollary HPAI as defined by OIE may still be confirmed in such birds

• Coverage rates in key at risk populations need to be >60% (ideally 80%)

• Infection with HPAI virus without clinical signs may lead to spread and an endemic situation

Vaccination will only work when applied in combination with other

measures

Vaccination is not a substitute for weak farm biosecurity

Challenges associated with use of vaccination

• Clearly defined objectives/Exit strategy• Supplementary tool for control of outbreaks

– Biosecurity– Stamping out of infected flocks– Buffer zones

• Proactive surveillance necessary in vaccinated populations– DIVA– Serological monitoring– Use of sentinels

• Antigenic variability in field strains• Target populations?• Ease of delivery• System for control of statutory disease needs to be subject to supervision by

competent veterinary authority• Trade impacts• Management of public health implications/assurance• Effective tool for control of HPAI?

Veterinary inactivated vaccines for AI (advantages and disadvantages)

• Inactivated whole AI virus – with adjuvant; produced versus field strain (ie rg viruses in China versus evolving H5)

• Relatively cheap, multiple hosts, easy to standardise, can be adapted to field virus, licensure

• Generally 2 doses for protection; NO mass application, lack DIVA, poor in overcoming maternal antibody, or hatchery application

Text in footer 15

Veterinary vectored vaccines for AI (advantages and disadvantages)

• Live vector – avian virus carrying an AI gene insert ie H5 HA

• Number of delivery vectors (Avian Avulavirus [APMV1] 1, DVE, Fowlpox, Herpesvirus Turkey

• Relatively cheap, easy to standardise, can be adapted to field virus, mass application including at hatchery, DIVA applicable

• Host specificity (define target population), licensure for field, natural immunity in population to vector

Text in footer 16

Veterinary other vaccines for AI (advantages and disadvantages)

• In vitro produced HA• Adaptable to changing virus, DIVA, multiple hosts• Poor knowledge for field application, expensive to

produce, delivery? • Nucleic acid

• Adaptable to changing virus, DIVA, multiple hosts• Poor knowledge for field application, expensive to

produce, delivery?, 2 doses minimum

Text in footer 17

APHA 2017 18

Text in footer 19

Mapping antigenic changes in H5 HPAI virusesp

2.3.4.4

2.3.2.1

20

H5 ANTIGENIC MAPPING 2.3.2.1 & 2.3.4.4

APHA-Weybridge; IZSVe, Padova; CSIRO, Geelong

Vaccination as a tool for prevention/control

• 114 billion doses (2002-2010) in 15 countries (42% average coverage)

• >99% in 4 countries; China (91%), Egypt (4.65%), Indonesia (2.3%) & Vietnam (1.43%)

• Ten countries or regions 0.7% of total (high risk targeting or management tool during eradication)

• Inactivated (95.5%) and live recombinant vectored vaccines (4.5%)

• Challenges to induce sufficient flock immunity in susceptible key species

• Used to achieve• Eradication followed by withdrawal of vaccination

21

Vaccination as a tool for prevention/control

• Used to achieve• Reduce disease burden without eradication (China, Egypt,

Indonesia, Vietnam)• Eradication followed by withdrawal of vaccination (ie Israel,

Coe d’Ivoire)• Eradication with continuation of vaccination as a

preventative measure (Hong Kong)• Preventative vaccination without HPAI in poultry

(Kazakhstan and Mongolia)

22

Potential application in a South Africa setting?

• Continual risk with epizootic waves

• Risk populations?

• Define aim

• Preventative- match to threat viruses; duration of programme?

• Emergency application to live (?) in buffer zones (?) as component of control strategy towards eradication

• delivery on scale challenges; time to induce flock immunity

Text in footer 23

Potential application in a South Africa setting?

• Challenges• Vaccine bank provision?• Ensure appropriate high quality vaccines• Efficacy versus changing virus• DIVA can be applied• Licensure issues• Cost benefit?

• Consider wider impacts• Trade, • Surveillance intensity/cost to prove freedom, • Vaccine escape• Public health perception/threat

Text in footer 24

Vaccination as a tool for prevention/controlSummary issues

• Although many vaccines are used few have proven utility to prevent H5 HPAI infection at population level

• Lack ease of delivery and efficacy versus a diverse family of viruses• Prime/boost (vector followed by inactivated)

• Innovations in vaccine design have largely not been invested in for AI for different field applications

• Universal vaccines?

• Target hosts: anseriformes present greatest challenge• Differentiating Infected from Vaccinated Animals

• Relevant for some areas/regions likely important for trade

• Produced in accord with international standards (OIE)• USA small vaccine stockpile since 14/15 epidemic

• rgH5N1 inactivated vaccine, RNA particle vaccine (i.e defective alphavirus vaccine) and recombinant HVT

APHA 2018 25

26APHA, SEPRL, OFFLU avian TA, CEIRS network

Step 1:antigenic and genetic analyses of currently circulating H5 clades

Influenzas of veterinary

public health importance

Step 3: quantitatively assess the

potential risk of emerging strains both between poultry and into humans

• Generate harmonised chicken and ferret serum panels

• HI assays with current H5 clade strains

• Antigenic cartography• Whole genome

sequencing• integrated phylogenetic

analyses

Step 2:evaluate antigenetic changes

of significance to both poultry vaccine efficacy and the transmission risk to and within mammalian species

Provide timely analyses to key stakeholder organisations:

Human Health ProfessionalsCompetent Veterinary AuthoritiesPoultry industry, Vaccine manufacturers, National and international advisory and

policy bodies, OIE and WHO, Inform pre-pandemic and poultry

vaccine strain selection, Risk assessment tools

Avian Influenza – One Health Assessment H5, H7 and H9 enhanced characterisation: next steps

Formalising a pipeline for risk assessment

APHA 2017 27

Acknowledgements

IRL, Animal and Plant Health AgencyNicola LewisSteve EssenNatalie McGinnJames SeekingsSusan CollinsHolly EverestSharon BrookesRichard Ellis, Bioinformatics, APHAHelen Roberts & team, IDM, APHA

Funding EURL- EU commission & Defra/UK DAs

OFFLU (OIE/FAO)EFSA/ECDCWHO CCs London & Atlanta

EU MS national reference labs for Avian InfluenzaThird countries sharing biologicals and data with APHA

Celia Abolnik, University of Pretoria

University of CambridgeNicola LewisDivya VenkateshSara Lopes

USDA-ARSAmy VincentErasmus MCRon Fouchier Marjolein PoenWHO/OFFLU H5 evolution working group

Thank you for your attentionVisit for AI situation reports

http://flu-lab-net.eu/

Email: aiwrl@apha.gsi.gov.uk