1. Influenza Virologic Surveillance and Vaccine Strain Selection Xiyan Xu MD Deputy Director WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza Virus Reference Team Virology, Surveillance and Diagnosis Branch Influenza Division, NCIRD Centers for Disease Control and Prevention Atlanta, Georgia U.S.A. Xiyan Xu MD Deputy Director WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza Virus Reference Team Virology, Surveillance and Diagnosis Branch Influenza Division, NCIRD Centers for Disease Control and Prevention Atlanta, Georgia U.S.A.

2. Virologic Surveillance Virologic surveillance is the foundation of influenza control efforts –Identify changes in circulating strains Future vaccine strain selection Assess current vaccine match Identify novel viruses with pandemic potential –Establish seasonality Timing of active surveillance Timing of influenza control activities

3. The Global Influenza Surveillance and Response System (GISRS) 143 Institutions in 113 WHO member states 6 WHO Collaborating Centers: United States (CDC, Atlanta) United Kingdom (NIMR, London) Australia (VIDRL, Melbourne) Japan (NIID, Tokyo) China (CCDC, Beijing) United States* (St. Jude, Memphis) *THE ECOLOGY OF INFLUENZA IN LOWER ANIMALS AND BIRDS 4 WHO Essential Regulatory Laboratories (ERLs) 13 WHO H5 Reference Laboratories.

4. Global influenza virological surveillance has been conducted through WHO's Global Influenza Surveillance and Response System (GISRS) for over half a century. WHO GISRS, formerly known as the Global Influenza Surveillance Network (GISN), monitors the evolution of influenza viruses and provides recommendations in areas including laboratory diagnostics, vaccines, antiviral susceptibility and risk assessment. WHO GISRS also serves as a global alert mechanism for the emergence of influenza viruses with pandemic potential. Global Influenza Surveillance and Response System (GISRS)

5. National Influenza Centers National Influenza Centers (NICs) collect virus specimens in their country and perform preliminary analysis. They ship representative clinical specimens and/or isolated viruses to WHO CCs for advanced antigenic and genetic analysis. The results form the basis for WHO recommendations on the composition of influenza vaccine each year, as well as relevant risk assessment activities of WHO. NICs are national institutions designated by national Ministries of Health and recognized by WHO. They form the backbone of the WHO's Global Influenza Surveillance and Response System (GISRS).

7. US CDC (Atlanta) NIMR (London) VIDRL (Melbourne) NIID (Tokyo) CCDC (Beijing) WHO collaborating centers (WHO CCs) for Reference and Research on Influenza

8. National Influenza Centers World Health Organization (Geneva) Vaccine Producers WHO Collaborating Centers Collect Specimens from ILI cases Isolate and Identify viruses Send viruses to a WHOcc Collect epidemiologic information Collect information for the Weekly Epidemiological Record and WWW for distribution Make annual vaccine recommendations Analyze influenza viruses received Provide data for annual vaccine recommendations Prepare and distribute candidate vaccine strains Global Influenza Surveillance and Response System (GISRS)

9. Virus Characterization at CDC Virus Propagation Hemagglutination Inhibition test (HI) Neutralization Focus Reduction assay(FRA) NGS genome Sequencing Antigenic Characterization Genetic Analysis Antiviral Susceptibility Assays Phenotypic-NAI Genotypic Diagnosis Confirmation RTPCR Report to sender Submit to GISAID Specimen Receipt Influenza + Summary report

10. Since 1973, WHO has provided formal recommendation for the composition of influenza vaccines based on the information provided by the WHO Global Influenza Surveillance Network (GISN), now the WHO Global Influenza Surveillance and Response System. Twice annually, WHO organizes consultations with an advisory group of experts to analyze influenza virus surveillance data generated by the WHO Global Influenza Surveillance and Response System (GISRS), and issues recommendation on the composition of the influenza vaccines for the following influenza season. These recommendations are used by the national vaccine regulatory agencies and the pharmaceutical companies to develop, produce and license influenza vaccines. WHO Consultation and Information Meeting on the Composition of Influenza Virus Vaccines

11. WHO consultation for southern hemisphere (SH) WHO consultation for northern hemisphere (NH) SH season NH season

12. Participants (by invitation) of the WHO Consultation Meeting 1.Representatives from the WHO Collaborating Centers for influenza (CCs) of GISRS; 2.Representatives from the WHO Essential Regulatory Laboratories (ERLs) of GISRS; 3.Representatives from National Influenza Centers and the WHO H5 Reference Laboratories of GISRS; 4.Experts on antigenic cartography; and 5.Representatives from the OIE/FAO Network of expertise on animal influenza (OFFLU).

13. Main agenda items of the WHO Consultation Meeting 1.Review of the global influenza activity; Review of vaccine effectiveness studies (if available) 2.Review of antigenic and genetic characterization data of seasonal, A(H5N1), A(H7N9) and other subtypes or variant influenza viruses analyzed by CCs and other reference laboratories; 3.Analysis of results of vaccine serological studies; 4.Recommendations for influenza vaccine composition for the following influenza season; 5.Review of the need and subsequent selection of new A(H5N1), A(H7N9) and other subtype or variant viruses for the development of new candidate vaccine viruses for pandemic preparedness purposes.

14. WHO Consultation: Data review and analysis Epidemiology Antigenic Characterization Genetic Analysis Human Serology

16. Evolutionary Relationships Among Influenza A(H1N1)pdm09 Hemagglutinin (HA) Genes 2015-2016 (CDC)

19. Antigenic cartography of A(H1N1)pdm09 viruses (U. Cambridge)

20. HI ANTIBODY RESPONSES TO THE A(H1N1)pdm09 COMPONENT (% GMT) relative GMT

21. Recommended composition of influenza virus vaccines for use in the 2016-17 northern hemisphere influenza season It is recommended that the following viruses be used for trivalent influenza vaccines in the 2016-2017 northern hemisphere influenza season: –an A/California/7/2009 (H1N1)pdm09-like virus; –an A/Hong Kong/4801/2014 (H3N2)-like virus; and –a B/Brisbane/60/2008-like virus. For quadrivalent vaccines containing 2 B components: –Above 3, plus –A B/Phuket/3073/2013-like virus

22. Questions? Thank you !