Predicting the future
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1 Swine influenza A viruses: a more global picture Predicting the future Dr Nicola S. Lewis BSc BVetMed PhD MRCVS Dr Nicola S. Lewis BSc BVetMed PhD MRCVS Centre for for Pathogen Evolution and WHO Collaborating Centre for for Modeling and Control of of Emerging Infectious Diseases Department of of Zoology University of of Cambridge
2 Antigenic and genetic diversity Estimated dates of introduction Reservoirs of infection Drivers of emergence Transmission and disease Lewis et al., submitted
3 Phenotype analyses Comparative analyses of factors involved ecology and evolution of swine IAV Herd-level and structure, age, immune status/vaccination, between and among countries/regions Relative human-swine contact rates in different production systems Vaccine efficacy (formulation and use), strain selection Competition among subtypes/ withinsubtype variants Relative risk of introduction to other pig pu populations and to humans
4 Swine Influenza- Pandemic Threats Concept Dr Amy Vincent (USDA) Dr Nicola Lewis (University of Cambridge) Adolfo Garcia-Sastre (Mt. Sinai)
5 Proposed swine RA pipeline Putative pipeline for assessing the risk of endemic swine IAV circulating globally to the human population. Swine isolates identified through surveillance and sequencing efforts will be selected to enter the pipeline. The cycle will be repeated annually or as needed as newly characterized swine IAV with antigenic distance from human seasonal viruses are identified.
6 Step 1 Swine-human antigenic distance CRIP: Amy Vincent NADC USDA swine surveillance sequence and antigenic analyses and CDC variant viruses. Raise swine sera to selected swine and human seasonal influenza viruses. Provide swine reference antisera and antigens to other Centres and participants -> St Jude s, Emory, Mt. Sinai. HI with swine strains using swine & ferret antisera. CRIP: Nicola Lewis University of Cambridge Antigenic cartography and phylogenetic analyses of swine viruses. Selection of reference panels in consultation with AV. Define and identify highly divergent swine strains in consultation with AV. CRIP: Adolfo Garcia-Sastre/Randy Albrecht HI with swine isolates obtained through CRIP with swine & ferret antisera. Raise ferret antisera to selected swine and human seasonal strains in consultation with NADC/Cambridge. Contribute highly divergent strains to the pipeline. Share ferret antisera panel with other CEIRS.
7 Step 1 continued Swine-human antigenic distance St Jude s: Richard Webby and Stacey Shultz Cherry HI with swine isolates obtained through SJCEIRS with panel of swine & ferret antisera. Raise ferret antisera to selected swine and human seasonal strains in consultation with NADC/Cambridge. Share ferret antisera panel with other CEIRS. Contribute highly divergent strains to the pipeline. Emory: Ralph Tripp/Mark Tompkins HI with swine isolates obtained through Emory CEIRS with panel of swine & ferret antisera. Contribute highly divergent strains to the pipeline. Non-CEIRS AHPA/ANSES: HI with swine isolates circulating in Europe against selected NADC swine antiserum and/or ferret antisera Contribute highly divergent strains to the pipeline. Share ferret antisera panel with other CEIRS..
8 Human Vaccine Strains for Swine Anti-sera Progress and Future Plans Subtyp Vaccine NADC Vaccine Strain Year e Season Sera A/California/04/ H1N Yes A/Brisbane/59/ H1N Yes A/Solomon Island/3/ H1N Yes A/ Michigan/02/ H1N2 N/A Yes A/New Caledonia/20/ H1N Yes A/Victoria/361/ H3N Yes A/Perth/16/ H3N Yes A/Brisbane/10/ H3N Yes A/Wisconsin/67/ H3N Yes A/Fujian/411/ H3N Yes A/Moscow/10/ H3N Yes A/Sydney/5/ H3N Yes A/Wuhan/359/ H3N Yes Comparison of influenza virus phenotype characterised using ferret and swine antisera NAD Subtyp Vaccine C Vaccine Strain Year e Season Sera A/Singapore/ H1N No A/Brazil/11/ H1N No Received from St. Jude No A/Beijing/262/ H1N1 A/Texas/36/ H1N No A/Taiwan/1/ H1N No A/Chile/1/ H1N No A/USSR/ H1N No A/Switzerland/ / H3N No A/Beijing/32/ H3N No A/Beijing/353/ H3N No A/Sichuan/02/ H3N No A/Shanghai/11/ H3N No A/Leningrad/360/ H3N No A/Philippines/2/ H3N No A/Bangkok/01/ H3N No A/Texas/1/ H3N No A/Victoria/3/ H3N No A/Port Chalmers/1/ H3N No
9 Step 2 Population immunity to swine strains JHCEIRS: Andy Pekosz Collect a stratified by age human serum panel from communitybased sampling in NY. Contribute a Taiwanese human serum panel. Characterise selected swine strains against the human serum panel and submit results for antibody landscaping. St Jude s: Richard Webby and Stacey Shultz-Cherry Contribute a South American human serum panel. Characterise selected swine strains against the human serum panel and submit results for antibody landscaping. CRIP: Nicola Lewis Produce antibody landscapes of human sera relative to selected highly divergent swine influenza viruses.
10 Step 3 Laboratory testing high risk swine strains SJCEIRS: Pathogenesis (mouse model and ferret) and pre-pandemic vaccine work CRIP: Pathogenesis in ferrets and other (Mt. Sinai) Receptor binding studies Vaccine efficacy studies (NADC) Emory: Receptor binding studies JHCEIRS: Andy Pekosz Infectivity studies in human primary respiratory epithelial cells Other Centers?
11 Step 4 Inform Public Health CRIP, SJCEIRS, Emory, JHCEIRS: Disseminate results through presentations, reports, & publications to key stakeholders. NIH-CEIRS CDC WHO USDA-APHIS Swine industry Veterinary biologics companies St. Jude: Richard Webby Share data at WHO Composition of Vaccine Meetings. Public Health: Candidate pandemic preparedness vaccine seed strains selected and developed as needed. Pilot lot vaccine production Clinical trials
12 The research leading to these results has received funding from the European Union s Seventh Framework Programme for research, technological development and demonstration under grant agreement n [259949]. USDA-ARS SCA agreement number F USDA-ARS SCA agreement number Colin Russell and Kathryn Berger Department of Veterinary Medicine, University of Cambridge David Burke, Judy Fonville and Eugene Skepner Ian Brown and Sharon Brookes and the ESNIP3 consortium UK T. Saito and Nobuhiro Takemae National Institute of Animal Health, Ibaraki, Japan Ron Fouchier and Bjorn Koel* Department of Zoology, University of Cambridge Erasmus MC - Department of Viroscience, Rotterdam, The Netherlands (*now at Department of Medical Microbiology, University of Amsterdam, The Netherlands) Animal Health and Plant Agency, Paul Kellam and Simon Watson Institute, Hinxton, UK Wellcome Trust Sanger G. Simon R. Webby K. Van Reeth Anses, Ploufragan-Plouzané Laboratory, Swine Virology Immunology Unit, France St. Jude Children s Research Hospital, Memphis, TN, USA Ghent University, Ghent, Belgium T. Nguyen Department of Animal Health, National Centre for Veterinary Diagnostics, Hanoi, Vietnam B. Nuansrichy Thailand National Institute of Animal Health, Bangkok, L. Larsen Denmark Technical University, Copenhagen, Denmark A. L. Vincent and Tavis Anderson ARS, Ames, USA M. Peiris Virus and Prion Research Unit, National Animal Disease Center, USDA- Hong Kong University, Hong Kong City, Hong Kong 12
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