Global Influenza Virus Surveillance and WHO Influenza Vaccine Virus Recommendations for the Northern Hemisphere Influenza Season

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Global Influenza Virus Surveillance and WHO Influenza Vaccine Virus Recommendations for the Northern Hemisphere 2015-16 Influenza Season Jacqueline Katz, Ph. D. Deputy Director (acting), Influenza Division Director, WHO COLLABORATING CENTER FOR SURVEILLANCE, EPIDEMIOLOGY AND CONTROL OF INFLUENZA Influenza Division, NCIRD, CDC National Adult and Influenza Immunization Summit Teleconference March 19, 2015

WHO Surveillance Network (GISRS) and Vaccine Virus Selection Year around surveillance conducted by the Global Influenza Surveillance and Response System (GISRS) 142 National Influenza Centers (NICs) in 112 countries, 6 WHOCCs, WHO Essential Regulatory Labs, H5 Reference Labs WHO Vaccine Consultation Meeting, 23-25 Feb 2015: Review and analysis of global data on viruses collected since Sept 1,2014 Data presented at VRBPAC Meeting March 4, 2015 Full slide set available on FDA website Considerations for new vaccine virus recommendations Are there new antigenic variants with signature genetic changes? Antigenic characterization (HI and VN assays) using ferret or human serum Genetic characterization: sequence analysis of HA and NA genes Are new variants spreading? Monitoring influenza disease activity and virus isolation Are current vaccines able to induce antibodies to the new variants? Are candidate vaccine viruses representing new variants available?

WHO information meeting on influenza vaccine composition for northern hemisphere 2015-2016 26 February 2015 EB Room WHO Geneva

Summary of A(H1N1)pdm09 Viruses A(H1N1)pdm09 activity was generally sporadic in Asia, Africa, the Americas, Europe, and was variable in Oceania. Local to widespread outbreaks occurred in Australia, New Caledonia, and New Zealand in September and October, 2014. The majority of circulating A(H1N1)pdm09 viruses belonged to genetic clade 6B. All of the A(H1N1)pdm09 viruses remained antigenically similar to the recommended vaccine virus A/California/7/2009.

(H1N1)pdm09 low reactors in HI assays by WHO CCs WHO CC A/Cal/07/09 Low ( 8 fold) CDC 33 (100%) 0 (0%) CNIC 36 (100%) 0 (0%) NIID 2 (100%) 0 (0%) NIMR 85 (100%) 0 (0%) VIDRL 213 (100%) 0 (0%) Total 369 (100%) 0

Antigenic cartography of A(H1N1)pdm09 viruses Gold: viruses from 2014 Blue: viruses from 2013 Grey: viruses before 2013 Large red dot: A/California/7/2009 From Derek Smith and Colin Russell, University of Cambridge, UK

A(H3N2) Summary Influenza A(H3N2) activity was generally sporadic in Africa and Oceania, but was regional to widespread in the Americas, Asia and Europe. A(H3N2) viruses collected from September 2014 to January 2015 fell into the phylogenetic clades 3C.2 and 3C.3. Antigenic characterization of A(H3N2) viruses has become technically difficult Many 3C.2a viruses had low or undetectable hemagglutination activity. The majority of recent A(H3N2) viruses were poorly inhibited by ferret antisera raised against egg- and cell-propagated reference A/Texas/50/2012 (clade 3C.1) viruses. Most viruses were well inhibited by ferret antisera raised against cell-propagated A/Switzerland/9715293/2013 (3C.3a) virus and representative cell-propagated 3C.2a viruses 3C.2a and 3C.3a viruses were antigenically related, but distinguishable in some cases Ferret antisera raised against egg-propagated A/Switzerland/9715293/2013 reacted well with most recently circulating viruses.

Global Distribution of H3 HA Clades

H3 low reactors in HI assays conducted by WHO CCs WHO CC A/Texas/50/2012 -like Low ( 8 fold) CDC 243 (37%) 413 (63%) CNIC 22 (4%) 532 (96%) NIID 7 (28%) 18 (72%) NIMR 84 (62%) 51 (38%) VIDRL 30 (17%) 143 (83%) Total 386 (27%) 1055 (73%)

From Derek Smith and Colin Russell, University of Cambridge, UK Cartography of HI Data from CDC

Influenza B Summary Influenza B activity was generally low world-wide B/Victoria and B/Yamagata lineage viruses co-circulated, with B/Yamagata viruses continuing to predominate. B/Yamagata lineage viruses: HA genes fell into genetic clades 2 and 3. The great majority of tested viruses belonged to clade 3. Recently circulating viruses were well inhibited by antisera raised against eggpropagated B/Phuket/3073/2013, the virus recommended for use in the 2015 southern hemisphere vaccine. B/Victoria lineage viruses: Of the low number of viruses tested, most were antigenically and genetically similar to B/Brisbane/60/2008 and belonged to genetic group 1A B/Texas/02/2013 is a B/Brisbane/60/2008-like genetic 1A group virus

Influenza B low reactors by lineage in HI assays in WHO CCs WHO CC Victoria Yamagata (B/Brisbane/60/2008) (B/Phuket/3073/2013) CDC 55 (90%) 170 (92%) Low Reactors 6 (10%) 13 (8%) CNIC 3 (15%) 201 (100%) Low Reactors 17 (85%) 0 (0%) NIID 1 (100%) 5 (100%) Low Reactors 0 (0%) 0 (0%) NIMR 10 (70%) 107 (100%) Low Reactors 4 (30%) 0 (0%) VIDRL 16 (100%) 36 (100%) Low Reactors 0 (0%) 0 (0%) Total (%) 112 (81%) 519 (98%) Low Reactors 27 (19%) 13 (2%)

From Derek Smith and Colin Russell, University of Cambridge, UK

Recommendation It is recommended that the following viruses be used for influenza vaccines in the 2015-2016 influenza season (northern hemisphere): an A/California/7/2009 (H1N1)pdm09-like virus; an A/Switzerland/9715293/2013 (H3N2)-like virus; a B/Phuket/3073/2013-like virus. For quadrivalent vaccines containing 2 B components: Above 3, plus A B/Brisbane/60/2008-like virus

Acknowledgements WHO Collaborating Centers in Beijing, Melbourne, London and Tokyo and WHO Geneva staff National Influenza Centers University of Cambridge partners Essential Regulatory Laboratories CDC staff including Xiyan Xu, Rebecca Garten, David Wentworth, John Barnes, Larisa Gubareva, Daniel Jernigan and many others