Influenza Virus Vaccine 2009-2010 Strain Selection

1. Influenza Virus Vaccine2009-2010 Strain Selection Jerry P. Weir, Ph.D. Director, Division of Viral Products CBER/FDA Prepared for Vaccines and Related Biological Products Advisory Committee 18 February 2009

2. Purpose of Today’s VRBPAC Committee Discussion • Make recommendations for the strains of influenza A (H1N1 and H3N2) and B viruses to be included in 2009-2010 influenza vaccines for use in the United States

3. Why Consider Strain Changes in Influenza Vaccines? Vaccine efficacy relates to: • Vaccine potency (immunogenicity) • Match of vaccine HA/NA with wild-type viruses • Antigenic drift of HA/NA continuous in influenza A and B viruses • Evidence of reduced vaccine effectiveness resulting from antigenic drift observed within 2 years after influenza vaccines first licensed for use in United States

4. Questions to Be Answered forStrain Changes Every Year • Are new (drifted or shifted) influenza viruses present? • Are these new viruses spreading in people? • Do current vaccines induce antibodies against the new viruses (HA)? • Are strains suitable for vaccines available?

5. Types of Analyses Used forVaccine Strain Selection • Antigenic relationships among contemporary viruses and candidate vaccine strains • Hemagglutination inhibition (HI) tests using post-infection ferret sera • Virus neutralization tests • HI tests using panels of sera from humans receiving TIV • Antigenic cartography • Phylogenetic analyses of HA and NA genes • Epidemiology of circulating strains • Availability and characteristics of egg-derived vaccine strains and high-growth reassortants

6. Review of Influenza Strain Selectionfor 2008-2009 • H1N1 • 2007-2008 vaccine contained an A/Solomon Islands/3/2006-like virus strain • By February 2008, an increasing % of H1N1 viruses were antigenically distinguishable from the vaccine strain • Recommendation was made to switch the H1N1 vaccine strain to an A/Brisbane/59/2007-like virus for 2008-2009 • H3N2 • 2007-2008 vaccine contained an A/Wisconsin/67/2005-like virus strain • By February 2008, an increasing % of H3N2 viruses were antigenically distinguishable from the vaccine strain Recommendation was made to switch the H3N2 vaccine strain to an A/Brisbane/10/2007-like virus for 2008-2009

7. Review of Influenza Strain Selectionfor 2008-2009 (Cont.) • B • 2007-2008 vaccine contained a B/Malaysia/2506/2004-like virus strain (B/Victoria lineage – 2nd consecutive year) • In February 2008, both lineages circulating, but B/Yamagata-like viruses predominated. Of the isolated B/Victoria-like viruses, increased heterogeneity to the vaccine strain observed. • Recommendation was made to switch the B vaccine strain to a B/Florida/4/2006-like virus (B/Yamagata lineage) for 2008-2009 • Vaccine situation during 2008-2009 influenza season • All three strain components changed from previous 2007-2008 NH vaccine • Recommendations for U.S. vaccine composition same as WHO • Preparation of vaccine was on schedule and supply plentiful

8. Current Licensed seasonal InfluenzaVaccines (U.S.) • Inactivated seasonal influenza vaccines • Fluzone (Sanofi-Pasteur) • Fluvirin (Novartis) • Fluarix (GSK) • FluLaval (ID Biomedical [GSK]) • Afluria (CSL) • Live attenuated seasonal influenza vaccine • FluMist (MedImmune)

9. Timelines for Vaccine Production

10. WHO Consultation on the Composition of Vaccines for the Northern Hemisphere, 2008-2009 • February 9-11, 2009 • Analyze the antigenic and genetic characteristics of seasonal influenza strains circulating globally, taking into consideration epidemiological data on influenza obtained from individual countries and regions. • Make recommendations on the composition of the influenza vaccine for the northern hemisphere 2009 - 2010. • www.who.int/csr/disease/influenza/recommendations2009_10north/en/index/html

11. WHO Recommendations for Influenza Vaccine CompositionNorthern Hemisphere: 2009-2010 • “It is recommended that vaccines for use in the 2009-2010 influenza season (northern hemisphere winter) contain the following: • an A/Brisbane/59/2007 (H1N1)-like virus • an A/Brisbane/10/2007 (H3N2)-like virus • a B/Brisbane/60/2008-like virus” • “As in previous years, national control authorities should approve the specific vaccine viruses used in each country” – VRBPAC and CBER

12. Committee Discussion • What strains should be recommended for the antigenic composition of the 2009-2010 influenza virus vaccine based on: • the epidemiology and antigenic characteristics of influenza virus strains circulating in human populations • the serologic responses to circulating influenza viruses of persons immunized with current influenza virus vaccines, and • the availability of suitable vaccine candidate strains

13. Options for Strain Composition for 2009-2010 Influenza Vaccines • Influenza A (H1N1) • Retain current vaccine strain A/Brisbane/59/2007 (H1N1)-like virus • e.g., A/Brisbane/59/2007; A/South Dakota/6/2007 • Replace current vaccine strain with alternative H1N1 isolate • Other candidates? • Influenza A (H3N2) • Retain current strain A/Brisbane/10/2007 (H3N2)-like virus • e.g., A/Brisbane/10/2007; A/Uruguay/716/2007 • Replace current vaccine strain with alternative H3N2 isolate • Other candidates? • Influenza B • Retain current B/Florida/4/2006-like virus (B/Yamagata lineage) • Replace current vaccine strain with alternative • B/Brisbane/60/2008-like virus (B/Victoria lineage) • e.g., B/Brisbane/60/2008; B/Brisbane/33/2008 • Other candidates?