Influenza Virus Vaccine 2012-2013 Strain Selection

1. Influenza Virus Vaccine2012-2013 Strain Selection Vaccines and Related Biological Products Advisory Committee (2/28/2012) Jerry P. Weir, Ph.D., Director Division of Viral Products/OVRR/CBER/FDA

2. Purpose of Today’s VRBPAC Committee Discussion • Review influenza surveillance and epidemiology data, antigenic characteristics of recent virus isolates, serological responses to current vaccines, and the availability of candidate vaccine strains and reagents • Make recommendations for the strains of influenza A (H1N1 and H3N2) and B viruses to be included in 2012-2013 influenza vaccines for use in the United States

3. Types of Analyses Used forVaccine Strain Selection • Epidemiology of circulating strains (CDC) • Surveillance data from U.S. and around the world • Antigenic relationships among contemporary viruses and candidate vaccine strains (CDC/DOD/CBER) • Hemagglutination inhibition (HI) tests using post-infection ferret sera • HI tests using panels of sera from humans receiving TIV • Virus neutralization tests • Antigenic cartography • Phylogenetic analyses of HA and NA genes • Vaccine effectiveness

4. Key Challenges for Vaccine Strain Selection • Vaccine effectiveness depends on match between the hemagglutinin (HA) of the vaccine and the HA of circulating strains of virus • Antigenic drift of HA continuous for influenza A and B • Antibody to HA correlated with vaccine efficacy • Timelines for influenza vaccine production are relatively fixed • Strain selection in February necessary for availability of vaccine for subsequent northern hemisphere winter (influenza season) • Manufacturers typically begin production of one monovalent before strain selection recommendations are made (at risk) • Availability of reference strains suitable for vaccine manufacture • Vaccine production depends on growth properties of strains used for manufacture • Strain-specific reagents needed for potency determination (inactivated vaccines)

5. Considerations for the Development of Quadrivalent Seasonal Influenza Vaccines • Two antigenically distinct lineages of influenza B co-circulate • Represented by B/Victoria/2/87 and B/Yamagata/16/88 • Quadrivalent influenza vaccines containing 2 B strains (one from each lineage) are relatively far along in development • Manufacturers can provide updates • Unique challenges • B viruses typically slow growing (hg reassortants not available) • Additional reagents needed • Relatedness between 2 lineages makes SRID and identity testing difficult • Process for selecting appropriate B strains for inclusion in trivalent and quadrivalent vaccines should follow the current process of strain selection • WHO and VRBPAC review and recommendations • All trivalent vaccines should contain same B vaccine strain • Decision regarding inclusion of a 2nd B strain should be data driven

6. 2011-2012 Seasonal Influenza Vaccine Strain Composition • VRBPAC strain selection – 2/22/2011 • Committee recommended the following strains for inclusion in U.S. 2010-2011 trivalent influenza vaccines • A/California/7/2009 (H1N1)-like virus • No change from the 2010-2011 vaccine recommendation • A/Perth/16/2009 (H3N2)-like virus • No change from the 2010-2011 vaccine recommendation • B/Brisbane/60/2008-like virus (B/Victoria lineage) • No change from 2010-2011 vaccine recommendation

7. WHO Recommendations for Influenza Vaccine CompositionNorthern Hemisphere: 2012-2013 • Recommended that the following viruses be used for influenza vaccines in the 2012-2013 influenza season (NH winter): • an A/California/7/2009 (H1N1) pdm09 - like virus • an A/Victoria/361/2011 (H3N2) - like virus • B/Wisconsin/1/2010 - like virus (B/Yamagata lineage) • For those considering the use of a B/Victoria/2/87 lineage vaccine virus, either in trivalent vaccines or in quadrivalent vaccines containing two influenza B viruses, B/Brisbane/60/2008-like viruses continue to be the appropriate vaccine virus • As in previous years, national or regional control authorities approve the composition and formulation of vaccines used in each country

8. Committee Discussion • Which influenza strains should be recommended for the antigenic composition of the 2012-2013 influenza virus vaccine in the U.S.? • Data to be considered includes: • the epidemiology of circulating influenza viruses • the antigenic characteristics of influenza virus strains currently circulating in human populations • the serologic responses to circulating influenza viruses of persons immunized with current influenza virus vaccines • manufacturing considerations including the availability of suitable vaccine candidate strains

9. Options for Strain Composition for 2012-2013 Trivalent Influenza Vaccines • Influenza A (H1N1) • Retain current vaccine strain A/California/7/2009 (H1N1)-like virus • Replace current vaccine strain with an alternative vaccine virus • Influenza A (H3N2) • Replace current vaccine strain with an A/Victoria/361/2011 (H3N2) - like virus • Replace current vaccine strain with another candidate vaccine virus or retain current vaccine strain A/Perth/16/2009 (H3N2)-like virus • Influenza B • Replace current vaccine strain with B/Wisconsin/1/2010 - like virus (B/Yamagata lineage) • Replace current vaccine strain with another candidate vaccine virus or retain current B/Brisbane/60/2008-like virus (B/Victoria lineage)

10. Options for Strain Selection for the 2nd Influenza B Strain in a Quadrivalent Influenza Vaccine • Influenza B • Include current vaccine strain B/Brisbane/60/2008-like virus (B/Victoria lineage) • Include another candidate vaccine virus of the B/Victoria lineage