Current limitations on the use of vaccination against avian influenza

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Alberta Dean
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Influenza, Newcastle Disease and Swine Influenza Animal and Plant Health

1 Current limitations on the use of vaccination against avian influenza Ian Brown Director of EU/OIE/FAO International Reference Laboratory for Avian Influenza, Newcastle Disease and Swine Influenza Animal and Plant Health Agency-Weybridge AVI AFRICA 2018, SAPA Conference & Exhibition June 2018 Gauteng

2 HPAI outbreaks

3 HPAI outbreaks poultry

4 HPAI H5N1 ancestral virus Goose/Guangdong/96

5 Multiple waves new strains virus constantly evolving (Goose/Guangdong lineage) Antigenetic change HA Accumulated changes Genotypic variation Genetic reassortment 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 spread to West Africa 2013 H5N2, H5N8, H5N6 ie clade spread to African continent Text in footer 5

6 APHA

3.2.1c 2.3.4.4 2.2.1 2.3.2.1a 2.3.2.1c 2.3.4.4 2.3.2.1c 2.3.4.4 2.3.2.1c 2.3.4.4 2.3.2.1c, 2.

7 HA Clade of H5 HPAI viruses isolated in October 2014 January c c a c c c c, a

8 Occurrence of HPAI in South Africa H5N2- locally derived 2017 H5N8 transcontinental spread 2018 H5N8 transcontinental spread 2019-??? Text in footer 8

9 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

10 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

11 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.

12 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

13 Vaccination will only work when applied in combination with other measures Vaccination is not a substitute for weak farm biosecurity

14 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

15 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

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

16 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

17 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

18 APHA

19 Mapping antigenic changes in H5 HPAI virusesp Text in footer 19

20 H5 ANTIGENIC MAPPING & APHA-Weybridge; IZSVe, Padova; CSIRO, Geelong 20

21 Vaccination as a tool for prevention/control 114 billion doses ( ) 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

22 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

23 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

24 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

25 Vaccination as a tool for prevention/control Summary 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

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

cartography Whole genome sequencing integrated phylogenetic analyses Step 1: antigenic and genetic

pipeline for risk assessment Step 2: evaluate antigenetic changes of significance to both poultry

assess the potential risk of emerging strains both between poultry and into humans 26 Influenzas of

Health Professionals Competent Veterinary Authorities Poultry industry, Vaccine manufacturers,

26 Avian Influenza One Health Assessment H5, H7 and H9 enhanced characterisation: next steps Generate harmonised chicken and ferret serum panels HI assays with current H5 clade strains Antigenic cartography Whole genome sequencing integrated phylogenetic analyses Step 1: antigenic and genetic analyses of currently circulating H5 clades APHA, SEPRL, OFFLU avian TA, CEIRS network Formalising a pipeline for risk assessment Step 2: evaluate antigenetic changes of significance to both poultry vaccine efficacy and the transmission risk to and within mammalian species Step 3: quantitatively assess the potential risk of emerging strains both between poultry and into humans 26 Influenzas of veterinary public health importance Provide timely analyses to key stakeholder organisations: Human Health Professionals Competent Veterinary Authorities Poultry industry, Vaccine manufacturers, National and international advisory and policy bodies, OIE and WHO, Inform pre-pandemic and poultry vaccine strain selection, Risk assessment tools

27 Acknowledgements IRL, Animal and Plant Health Agency Nicola Lewis Steve Essen Natalie McGinn James Seekings Susan Collins Holly Everest Sharon Brookes Richard Ellis, Bioinformatics, APHA Helen Roberts & team, IDM, APHA Funding EURL- EU commission & Defra/UK DAs Celia Abolnik, University of Pretoria University of Cambridge Nicola Lewis Divya Venkatesh Sara Lopes USDA-ARS Amy Vincent Erasmus MC Ron Fouchier Marjolein Poen WHO/OFFLU H5 evolution working group OFFLU (OIE/FAO) EFSA/ECDC WHO CCs London & Atlanta EU MS national reference labs for Avian Influenza Third countries sharing biologicals and data with APHA APHA

28 Thank you for your attention Visit for AI situation reports

Vaccines of today and products needed for the short-, intermediate- and longterm. OIE/FAO OFFLU Conference Beijing China December 4-6, 2013

Vaccines of today and products needed for the short-, intermediate- and longterm XU, Wei-Cheng OIE/FAO OFFLU Conference Beijing China December 4-6, 2013 1 Influenza A reservoir & transmission H3N8, (H5N1)