1. INFORMATION FOR THE VACCINE AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE CBER, FDA Information Regarding Seasonal Influenza Viruses FEBRUARY 27, 2013 Nancy J. Cox, Ph. D. Director, Influenza Division Director, WHO COLLABORATING CENTER FOR SURVEILLANCE, EPIDEMIOLOGY AND CONTROL OF INFLUENZA Influenza Division National Center for Immunization and Respiratory Diseases Coordinating Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta, GA 30333

2. Global Influenza Surveillance and Response Network (GISRS) All year around surveillance conducted by GISRS –6 WHOCCs, 140 NICs, 4 ERLs, H5 Reference Laboratories 18-20 Feb 2013 WHO Consultation: Data review and analysis; write recommendations Co-Chaired by Dr. Nancy Cox, WHOCC CDC Atlanta and Dr. Masato Tashiro, WHOCC, NIID Tokyo –9 Advisers: Directors of WHOCCs and ERLS Disclosure of potential conflicts of interest 18 observers from NICs, H5 Reference Laboratories, WHOCCs, WHO ERLs, academic partners and the veterinary sector

3. Influenza B – September 2012-January 2013 maximum influenza activity

4. Percentage of influenza viruses by subtypes (From 2 September 2012 – 2 February 2013) A(H5), 6 human viruses Data source: FluNet, (www.who.int/flunet), Global Influenza Surveillance and Response System (15 February 2013)www.who.int/flunet

5. Type and Subtype OseltamivirZanamivir Tested (n) Normal Reduced Highly Reduced Tested (n) Normal Reduced Highly Reduced US viruses:121812151b1b 2c2c 1217 00 A(H1N1)pdm0981790280 00 A(H3N2)767 00 00 B37036910370 00 Non-US viruses:153 00 00 A(H1N1)pdm0973 00 00 A(H3N2)14 00 00 B66 00 00 a Viruses were tested in the fluorescent NA inhibition assay. Inhibition is based on fold difference in IC 50 of a test virus compared to the median IC 50 value for type/subtype. The WHO AVWG criteria: Type A viruses - Normal: 100-fold.Type B viruses - Normal: 50-fold. b Influenza B/Maryland/07/2012 virus, GISIAD acc.no for NA: EPI399661. c H275Y was detected in two A(H1N1)pdm09 viruses. Susceptibility to Neuraminidase Inhibitors: Inhibition of Neuraminidase Activity a Virus collection period: Oct 01, 2012 - Jan 21, 2013

6. A(H1N1)pdm09 Viruses Sept 2012 – Jan 2013

7. Number of A(H1N1)pdm09 Viruses Detected by GISRS Data source: FluNet, (www.who.int/flunet), Global Influenza Surveillance and Response System (15 February 2013)www.who.int/flunet

9. (H1N1)pdm09 Viruses Characterized During the Past 3Years, September to January

10. (H1N1)pdm09 low reactors in HI assays by WHO CCs WHO CCA/Cal/7/09Low (≥ 8 fold) CDC 152 (95%)8 (5%) CNIC 120 (98%) 2 (2%) NIID 8 (99%) 1 (1%) NIMR 94 (98%) 2 (2%) VIDRL 18 (100%) 0 (0%) Total 392 (96.8%) 13 (3.2%)

11. REFERENCE FERRET ANTISERA 567 EGGMDCKEGGMDCKHASEQ.DATE REFERENCE ANTIGENSCA/7FL/27MD/13BA/2021 WA/24 CO/14GROUPCHANGECOLL. PASS. 1A/CALIFORNIA/7/2009*1280 1606401280 256004/09/09 E3 2A/FLORIDA/27/20112560 3206402560 510/30/11 E4 3A/MARYLAND/13/20121280 803201280 2560604/01/12 M1/C2 4A/BANGLADESH/2021/2012*408040320 160403206N156S07/21/12 E4 5A/BANGLADESH/2021/2012408040320 160203206N156S07/21/12 C1/C4 6A/WASHINGTON/24/2012*1280 160320256012802560706/17/12 E4 7A/WASHINGTON/24/20121280 803201280 640706/17/12 C3 8A/COLORADO/14/20121280 8032025601280 703/28/12 C1/C2 TEST ANTIGENS 9A/FLORIDA/60/20121280 801601280 256012/18/12 C1 10A/MINNESOTA/28/20121280 801601280 256012/09/12 C2 11A/MINNESOTA/30/20121280 803201280 256012/23/12 C1 12A/OHIO/106/20121280 806401280 256011/29/12 C2 13A/MINNESOTA/29/2012640 803201280 12/08/12 C2 14A/PENNSYLVANIA/30/2012640 1280403201280 2560612/04/12 C2 15A/WISCONSIN/49/2012640 80160640 128011/11/12 C2 16A/WYOMING/30/2012640 1280801601280640128012/19/12 C2 17A/WYOMING/31/2012@6401280640803201280 25607H275Y/NA12/26/12 C1 18A/NEW JERSEY/11/2012320 64040160640 128012/08/12 C2 19A/NORTH CAROLINA/29/2012320 2080320 640612/27/12 M1/C1 20A/TEXAS/99/2012320 64020160640 12806 12/17/12 M1/C1 21A/CHIANG RAI/312/2012*1280 25601606402560 610/02/12 C2/C2 22A/INDIA/2181/201212806401280801601280 2560612/21/12 C1 23A/INDIA/2192/20121280 1606401280 2560612/22/12 E3 24A/INDIA/2243/201212806401280801601280 256012/28/12 C1 25A/BANGLADESH/0019/2012640 80320640 128009/18/12 C2 26A/INDIA/2055/201264032064080320640 1280612/03/12E3 27A/INDIA/2055/2012640 40320640 1280612/03/12C1 28A/INDIA/2080/2012640 1280803201280 612/06/12C1 29A/INDIA/2192/2012*6401280 803201280 2560612/22/12C1 30A/INDIA/2205/2012640 128080320640 2560612/24/12E3 31A/INDIA/2227/2012640 128040160640 12806 12/25/12C1 32A/BANGLADESH/5011/2012160 32040160320 709/26/12C2 33A/INDIA/2150/2012160 80320 1603206 12/17/12C2 Sequence in GISAID * Serology antigen @ Oseltamivir resistant All but 2 viruses tested were well inhibited by ferret antisera raised against A/California/07/2009 and other recent reference viruses. The 2 low reactors did not acquire changes at positions153-157. HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA A(H1N1)pdm09 VIRUSES (01/23/13)

12. REFERENCE FERRET ANTISERA 567 X-179HASEQ.DATE REFERENCE ANTIGENSCA/7 FL/27MD/13BA/2021 WA/24 CO/14GROUPCHANGECOLL.PASS. 1A/CALIFORNIA/07/2009*128016064012801603201280 256004/09/09E3 2A/CALIFORNIA/07/2009 X-179320 80160 64032080320G155EREASS.EX/E2 3A/FLORIDA/27/20112560160128025603206402560 510/30/11E4 4A/MARYLAND/13/20121280806401280801601280 2560604/01/12M1/C2 5A/BANGLADESH/2021/2012*16080160 640 320160320607/21/12E4 6A/BANGLADESH/2021/201280408040320 8040160607/21/12C1/C4 7A/WASHINGTON/24/2012*64080640 80160640 1280706/17/12E5 8A/WASHINGTON/24/20121280801280 801601280 706/17/12C3 9A/COLORADO/14/201264080640 4080640 1280703/28/12C1/C2 TEST ANTIGENS 10A/GEORGIA/01/20131280801280 801601280 256001/02/13C1 11A/MASSACHUSETTS/01/2013128080640 8041601280 701/02/13M1/C1 12A/MASSACHUSETTS/02/2013128080640 801601280 701/02/13M1/C1 13A/PENNSYLVANIA/34/20121280801280 801601280 12/20/12C2 14A/TENNESSEE/09/20121280801280 801601280 610/31/12C3 15A/TEXAS/106/2012128080640 801601280 712/15/12C1 16A/WISCONSIN/01/2013128080640 801601280 01/06/13C1 17A/WISCONSIN/02/20131280801280 801601280 01/02/13C1 18A/HAWAII/42/201264080640 80160640 12/02/12M2/C1 19A/HAWAII/43/201264080640128080160640128064012/04/12M2/C1 20A/NEW YORK/01/201364080640 80160640 1280601/07/13C2 21A/NEW BRUNSWICK/RV0041/20121280806401280801601280 12/02/12X1/C1 22A/ONTARIO/RV0013/2012128080640 801606401280 12/12/12X1/C1 23A/ONTARIO/RV3144/2012128080640 801601280 64012/03/12X1/C1 24A/ONTARIO/RV3149/2012128080640 801601280 64012/12/12X1/C1 25A/NEW BRUNSWICK/RV0040/201264080640 80160640 12/03/12X1/C1 26A/INDIA/2139/20122560801280 801601280 12/17/12C2 27A/TANZANIA/2085/20122560160128025601603201280 256012/10/12C2 28A/INDIA/2019/20121280806401280401606401280 11/26/12C1 29A/INDIA/2080/201212801601280 1603201280 2560612/06/12E4 30A/INDIA/2171/20121280801280 1603201280 2560612/19/12E4 31A/INDIA/2181/201212801601280 803201280 612/21/12E4 32A/INDIA/2192/201212801601280 1603201280 2560612/22/12E4 33A/TANZANIA/2074/20121280801280 803201280 712/05/12C2 34A/TANZANIA/2081/20121280801280 801601280 12/03/12C2 35A/TANZANIA/332/20121280801280 801601280 12/11/12C1 36A/TANZANIA/339/20121280801280 801601280 12/18/12C1 37A/INDONESIA/PAL102/2012160 3206403201603206G155E08/24/12C2/C1 Sequence in GISAID * Proposed serology antigen HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA A(H1N1)pdm09 VIRUSES (01/29/13)

13. Antigenic Cartography of A(H1N1)pdm09 Viruses Sept 2012 to Feb 2013 – Gold, Aug 2011 to Aug 2012 – Blue, Earlier – Grey A/California /07/2009

14. A/California/07/2009 Apr # F $ NYMC X179A A/California/07/2009 # F NYMC X181 A/California/07/2009 # nimr A/Dakar/20/2012 Dec A/Cote DIvoire/1575/2013 Jan A/Nigeria/7781/2012 Oct A/Minnesota/16/2012 Oct A/Minnesota/03/2011 Feb F A/Minnesota/03/2011 Feb # F afrims A/Thailand/KPPH-00066/2012 niid A/Laos/I650/2012 Aug @ * namru2 A/Cambodia/FSS23932/2012 Dec A/Chiang Rai/312/2012 Oct $ nimr A/Netherlands/507/2012 Aug @ cnic A/Jilin-Chaoyang/SWL1709/2012 Dec A/Bangladesh/2021/2012 Jul LR # F C$ A/Bangladesh/2021/2012 Jul LR F nimr A/Ukraine/3/2013 Jan A/Florida/02/2013 Jan A/Wisconsin/02/2013 Jan A/India/2192/2012 Dec # F A/India/2192/2012 Dec F $ A/India/2150/2012 Dec LR A H1pdm09 HA Consensus 2012-13 nimr A/Norway/35/2013 Jan nimr A/England/658/2012 Dec A/New York/01/2013 Jan A/Gansu-Ganzhou/33/2012 Nov # hk A/Hong Kong/62/2013 Jan A/Tanzania/340/2012 Dec # A/Utah/01/2013 Jan A/Cote DIvoire/1529/2012 Dec # A/Oman/412/2012 Dec usafsam A/NewYork/1428/2013 Jan A/Georgia/01/2013 Jan # cnic A/Beijing/SWLChaoyang-P031/2013 Jan LR usafsam A/Korea/1419/2013 Jan A/Japan/1419/2013 Jan A/Washington/24/2012 Jun @ # F $ A/Washington/24/2012 Jun @ F namru6 A/Peru/FPI03819/2012 nhrc A/SouthCarolina/x88/2012 usafsam A/SouthCarolina/22/2012 Oct A/Wyoming/31/2012 Dec @ afrims A/Nepal/NPBH-00402/2012 afrims A/Bhutan/BTA-00098/2012 A/Tanzania/2085/2012 Dec # nimr A/Ghana/DILI-0902/2012 Oct cnic A/Beijing-Huairou/SWL11348/2012 Dec niid A/Yokohama/1/2013 Jan * A/Massachusetts/02/2013 Jan usafsam A/SouthDakota/1411/2013 Jan A/California/09/2013 Jan hk A/Hong Kong/9259/2012 Dec A/Ohio/02/2013 Jan Evolutionary Relationships Among Influenza A (H1N1)pdm09 Hemagglutinin (HA) Genes, 2012-13 02/22/2013 Current Northern Hemisphere Vaccine Strain LR- Low Reactor to A/California/07/2009 Egg (≥ 8 fold) F - CDC Reference Antigen $- CDC Serology Antigen C$- Common Serology Antigen @ - Oseltamivir Resistant # Egg Isolate * – only HA1 region October 2012 November 2012 December 2012 January 2013 7 5 8 6 HA Genetic Groups Since September 2012 S185T S451N P83S S203T I321V E374K A197T S143G K163I V520A S84G D97N K283E E499K H138R V249L V234I H51N I295V R205K V249L I216V A186T V272A N473D T474K V520A N156S N125S K163Q A256T I116M R205K S69T N260D V520A K154K/E

15. Evolutionary Relationships Among Influenza A (H1N1)pdm09 Neuraminidase (NA) Genes, 2012-13 02/22/2013 Current Northern Hemisphere Vaccine Strain LR- Low Reactor to A/California/07/2009 Egg (≥ 8 fold) F - CDC Reference Antigen $- CDC Serology Antigen C$- Common Serology Antigen @ - Oseltamivir Resistant H275Y # Egg Isolate HA Genetic Group Shown October 2012 November 2012 December 2012 January 2013 niid A/Yokohama/1/2013 Jan A/Ohio/02/2013 Jan A/California/09/2013 Jan A/Massachusetts/02/2013 Jan cnic A/Beijing-Huairou/SWL11348/2012 Dec nimr A/Ghana/DILI-0902/2012 Oct A/Tanzania/2085/2012 Dec # A/Georgia/01/2013 Jan # A/Cote DIvoire/1529/2012 Dec # nimr A/England/658/2012 Dec A/New York/01/2013 Jan nimr A/Norway/35/2013 Jan A/India/2150/2012 Dec LR A/Wisconsin/02/2013 Jan A/Utah/01/2013 Jan A/Tanzania/340/2012 Dec # A N1pdm09 NA Consensus 2012-13 A/Oman/412/2012 Dec A/India/2192/2012 Dec F $ A/India/2192/2012 Dec # F A/Florida/02/2013 Jan A/Gansu-Ganzhou/33/2012 Nov # A/Washington/24/2012 Jun @ # F $ A/Washington/24/2012 Jun @ F A/Wyoming/31/2012 Dec @ A/Japan/1419/2013 Jan cnic A/Beijing/SWLChaoyang-P031/2013 Jan LR A/Minnesota/03/2011 Feb # F A/Minnesota/03/2011 Feb F A/Chiang Rai/312/2012 Oct $ niid A/Laos/I650/2012 Aug @ nimr A/Netherlands/507/2012 Aug @ cnic A/Jilin-Chaoyang/SWL1709/2012 Dec A/Minnesota/16/2012 Oct nimr A/Ukraine/3/2013 Jan A/Bangladesh/2021/2012 Jul LR # F C$ A/Bangladesh/2021/2012 Jul LR F A/Nigeria/7781/2012 Oct A/Cote DIvoire/1575/2013 Jan nimr A/Dakar/20/2012 Dec A/California/07/2009 Apr # F $ NYMC X179A A/California/07/2009 # F NYMC X181 A/California/07/2009 # 7 5 8 6 7 6 G41R N44S ADD GLY L40V I106V N200S N248D V241I N369K D451G N222D N386S LOSS GLY N386K LOSS GLY V106I F74V N385T N44S ADD GLY

16. Summary - 1 A(H1N1)pdm09 viruses co-circulated in varying proportions along with A(H3N2) and B viruses. Regional A(H1N1)pdm09 activity was reported by a few countries in Asia and Central America. An increase in activity was reported, with regional and widespread outbreaks in January in many countries in Europe. Widespread outbreaks were reported in Algeria in January. Localized and sporadic influenza activity were reported in many other countries in northern Africa, Asia and North America.

17. Most A(H1N1)pdm09 viruses were antigenically similar to the recommended vaccine virus A/California/7/2009. Most recent A(H1N1)pdm09 viruses belong to genetic Clades 6 and 7. The majority of A(H1N1)pdm09 viruses were sensitive to oseltamivir. Of the small number of viruses that were resistant to oseltamivir, all had the H275Y mutation. Summary - 2

18. A(H3N2) Viruses Sept 2012 – Jan 2013

20. Number of A(H3N2) Viruses Detected by GISRS Data source: FluNet, (www.who.int/flunet), Global Influenza Surveillance and Response System (15 February 2013)www.who.int/flunet

21. H3N2 Viruses Characterized During the Past 3 Years from September to January USAChinaJapanUKAustralia

22. H3 low reactors in HI assays by WHO CCs WHO CCA/Vic/361/11 (MDCK) Low (≥ 8 fold) CDC 761 (99%)5 (1%) CNIC 829 (100%) 0 (0%) NIID 88 (98%)2 (2%) NIMR 115 (95%)6 (5%) VIDRL 117 (100%) 0 (0%) Total1923 (97%) 13 (3%)

24. REFERENCE FERRET ANTISERA 3C EGGMDCKEGGMDCKHASEQDATE REFERENCE ANTIGENSVIC/361 TX/50 GROUPCHANGESCOLL.PASS. 1A/VICTORIA/361/20111280320 3CH156Q, G186V,S219Y 1 10/24/11E3/E3 2A/VICTORIA/361/201140160 3C10/24/11C2/C3 3A/TEXAS/50/20126401280640 3C T128N, G186V, S198P, S219F 2 04/15/12E5 4A/TEXAS/50/201240160 3C T128N, S198P 2 04/15/12M1/C2 5A/TEXAS/50/2012 X-223640 320 3C I226N 3 REASS 6A/TEXAS/50/2012 X-223A640 320 3C I226N 3 REASS TEST ANTIGENS 4 7A/ARKANSAS/05/201280640320 3A12/19/12C2 8A/VIRGINIA/03/201380320 3CT128A, R142G, N145S 2 01/04/13C2 9A/NEW HAMPSHIRE/21/201240160 3CT128A, R142G, N145S 2 12/14/12R1/C1 10A/SOUTH CAROLINA/16/201280160 511/07/12M1/C2 11A/KANSAS/16/20122080 3CT128A, R142G, N145S 2 12/12/12C1 12A/MASSACHUSETTS/15/20124080 3CT128A, R142G, N145S 2 12/18/12C1 13A/COTE D'IVOIRE/1331/201280160 32011/07/12X/C1 14A/SAPPORO/125/201240160 3CN145S 3 11/01/12C1/C1 15A/HUBEI-HONGSHAN/1368/201280160 3CN145S 3 09/26/12C4/C2 16A/JIANGSU-XIUCHENG/1358/2012801603201603CT128A, R142G, N145S 3 09/04/12C3/C2 17A/LAOS/717/20128032016032009/17/12C2/C1 18A/LAOS/727/201280160 09/17/12C1/C1 HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA H3 VIRUSES (GUINEA PIG RED BLOOD CELLS) (01/24/13) 1. Egg-propagated A/Victoria/361/2011 differs from the cell-propagated A/Victoria/361/2011 at the 3 positions indicated. 2. Substitution in the HAs of the clade 3C viruses compared to cell-propagated A/Victoria/361/2011. 3. Substitution in the HAs of the A/Texas/50/2012 reassortants compared to egg-propagated A/Texas/50/2012. 4. All test viruses were cell-propagated.

25. Neutralization titer Post infection ferret sera VirusesA/StockholmA/AthensA/Vic Collection Passage18/11112/12361/11 Date History T/C F28/11T/C F16/12Egg F35/12T/C F14/12 Genetic group group 3Agroup 3Bgroup 3C REFERENCE VIRUSES A/Stockholm/18/20113A3/28/2011MDCK2/SIAT4160 40 A/Athens/112/2012 3B 2/1/2012SIAT416032040160 A/Victoria/361/2011 3C 10/24/2011E3/E2801605120320 A/Victoria/361/2011 3C 10/24/2011MDCK2/SIAT54016040320 A/Texas/50/2012 3C 4/15/2012E5/E1320640320640 TEST VIRUSES A/England/565/20123B5/31/2012SIAT2/SIAT63206403201280 A/England/587/20123C (128, 142)10/31/2012SIAT1/SIAT1320640160640 A/England/586/20123C (128, 142)11/2/2012SIAT1/SIAT1320640320640 A/Austria/705367/2012511/6/2012SIAT1/SIAT1160640160640 A/England/593/20123C (128, 142)11/12/2012SIAT1/SIAT1320640160640 A/Thuringen/33/123C11/12/2012C2/SIAT13206403201280 A/Cairo/59/20123B12/6/2012C1/SIAT1160320160320 A/Norway/2496/20123C12/10/2012SIAT1160320160320 A/Austria/710638/2012512/11/2012SIAT1/SIAT1160320160640 A/Cairo/81/20133B12/11/2012C1/SIAT180320160320 Antigenic Analysis of Influenza A(H3N2) Viruses - Plaque Reduction Neutralization (MDCK-SIAT)

26. Passage< 4-fold>8 foldtotal tested n%n%n VIC/361C2/C344699%31%449 VIC/361E3/E38519%36481%449 VIC/361 IVR-165EX/E200%10100%10 TX/50M1/C2449100%00%449 TX/50E537283%7717%449 HI/22C3448>99%1<1%449 HI/22E422951%21047%449 Summary of fold differences between reference viruses and test antigens in HI assays performed by CDC since January 2013

27. Sept 2012 to Feb 2013 – Gold, Aug 2011 to Aug 2012 – Blue, Earlier – Grey A/Victoria/361/2011-cell A/Victoria/361/2011-egg Antigenic Cartography of A(H3N2) Viruses A/Perth/16/2009

28. H3N2 Hemagglutinin changes compared to A/Victoria/361/2011-cell Victoria/361/2011 cell grown $ Receptor binding site Glycosylation site Antigenic site B Antigenic site D Antigenic site C Antigenic site E Antigenic site A G186V H156Q S219Y Victoria/361/2011 egg grown $ @ 3C

29. Texas/50/2012 cell grown $^ T128N 180° rotation Q33R N278K S198P ¥ N126 Texas/50/2012 egg grown $ @ S219F G186V H3N2 Hemagglutinin changes compared to A/Victoria/361/2011-cell

30. G186V I226S

31. A/Texas/50/2012 Apr # F $ A/Perth/16/2009 # F A/Jiangsu-Danyang/1647/2012 Oct # A/Jiangsu-Donghai/57/2012 Sep # A/Puerto Rico/36/2012 Jun # F A/Virginia/16/2012 Dec # A/Brisbane/299/2011 Aug # F usafsam A/Florida/1378/2013 Jan nimr A/Austria/710638/2012 Dec A/Delaware/23/2012 Dec # A/South Carolina/16/2012 Nov $ A/Florida/01/2013 Jan usafsam A/Texas/1406/2013 Jan A/Tanzania/303/2012 Nov A/Arkansas/05/2012 Dec A/Alaska/24/2012 Oct # A/Ohio/02/2012 Mar F A/Ohio/02/2012 Mar # F A/Ohio/02/2012 X-221 # F namru2 A/Cambodia/FSS23444/2012 Nov nimr A/Ukraine/551/2012 Dec nimr A/Cairo/136/2012 Dec A/Victoria/361/2011 Oct F $ A/Victoria/361/2011 IVR-165 # F A/Victoria/361/2011 Oct # F $ A/Hawaii/22/2012 Jul F $ A/Hawaii/22/2012 Jul # F A/Texas/50/2012 Apr F $ A/Texas/50/2012 X-223A # F A/Texas/50/2012 X-223 # F A H3 HA Consensus 2012-13 A/Seoul/3531/2012 Dec A/Delaware/01/2013 Jan LR A/Delaware/15/2012 Nov F $ niid A/Yokohama/164/2012 Dec * A/Arizona/09/2012 Oct # F A/California/04/2013 Jan usafsam A/Washington/1531/2013 Jan namru2 A/Cambodia/FSS22141/2013 Nov A/North Carolina/02/2013 Jan A/Ontario/RV2944/2012 Nov cnic A/Heilongjiang-Xiangfang/11272/2012 Dec * nimr A/Sachsen/2/2013 Jan usafsam A/Florida/1324/2013 Jan usafsam A/Guam/1490/2012 Dec lrmc A/Italy/x178/2013 Jan A/Illinois/01/2013 Jan usafsam A/DistrictofColombia/1414/2013 Jan nhrc A/Illinois/NHRC367623/2012 Dec * A/Ohio/01/2013 Jan A/South Dakota/12/2012 Oct # usafsam A/Virginia/1373/2013 Jan A/New York/03/2013 Jan A/North Dakota/08/2012 Dec nimr A/England/676/2012 Dec A/Montana/01/2013 Jan usafsam A/SouthDakota/1410/2013 Jan usafsam A/Alabama/1197/2013 Jan A/Colorado/27/2012 Dec A/Oregon/15/2012 Dec A/Nebraska/02/2013 Jan cnic A/Beijing-Huairou/128/2013 Jan * A/Virginia/03/2013 Jan nimr A/Athens GR/14/2013 Jan A/Rhode Island/02/2013 Jan A/Yamaguchi/30/2012 Oct LR usafsam A/NewYork/1365/2013 Jan A/New York/39/2012 Oct # A/West Virginia/01/2013 Jan lrmc A/Qatar/x119/2013 Jan A/Beijing-Xicheng/12423/2012 Oct $ usafsam A/Georgia/1407/2013 Jan A/Oklahoma/03/2013 Jan A/North Carolina/01/2013 Jan Evolutionary Relationships Among Influenza A (H3N2) Hemagglutinin (HA) Genes, 2012-13 3C.1 3B 6 3A 5 A/Perth/16/09- like 1 3C.2 3C.3 3C K62E K144N ADD GLY T212A P162S I260M R261Q D53N Y94H I230V E280A S199A K2E N8D LOSS GLY N144D LOSS GLY N145S D487N L3I D53N N145S D487N N144K LOSS GLY V223I A198S N312S S45N ADD GLY T48I Q33R N278K N145S T128A LOSS GLY R142G D489N R33Q H156Q G186V S219Y T128N LOSS GLY A198P G186V S219F I226N HA Genetic Groups Since September 2012

32. Evolutionary Relationships Among Influenza A (H3N2) Neuraminidase (NA) Genes, 2012-13 A/New York/39/2012 Oct # A/West Virginia/01/2013 Jan A/Rhode Island/02/2013 Jan A/Virginia/03/2013 Jan A/North Carolina/01/2013 Jan A/Oklahoma/03/2013 Jan nimr A/England/676/2012 Dec nimr A/Sachsen/2/2013 Jan A/Ontario/RV2944/2012 Nov cnic A/Beijing-Huairou/128/2013 Jan cnic A/Heilongjiang-Xiangfang/11272/2012 Dec A/North Dakota/08/2012 Dec A/Ohio/01/2013 Jan A/Illinois/01/2013 Jan A/Yamaguchi/30/2012 Oct LR A/Delaware/15/2012 Nov F $ niid A/Yokohama/164/2012 Dec A N2 Consensus 2012-13 A/Delaware/01/2013 Jan LR A/Seoul/3531/2012 Dec cnic A/Beijing-Xicheng/12423/2012 Oct $ A/Oregon/15/2012 Dec A/Montana/01/2013 Jan A/Nebraska/02/2013 Jan A/Hawaii/22/2012 Jul # F A/Hawaii/22/2012 Jul F $ A/North Carolina/02/2013 Jan A/Texas/50/2012 Apr # F $ A/Texas/50/2012 X-223A # F A/Texas/50/2012 Apr F $ A/Texas/50/2012 X-223 # F A/Victoria/361/2011 IVR-165 # F A/Victoria/361/2011 Oct # F $ A/Victoria/361/2011 Oct F $ A/Ohio/02/2012 Mar # F A/Ohio/02/2012 Mar F $ nimr A/Cairo/136/2012 Dec nimr A/Ukraine/551/2012 Dec A/South Carolina/22/2012 Nov A/Virginia/16/2012 Dec # A/Puerto Rico/36/2012 Jun # F nimr A/Austria/710638/2012 Dec A/Delaware/23/2012 Dec # A/Florida/01/2013 Jan A/South Carolina/16/2012 Nov $ A/Brisbane/299/2011 Aug # F A/Tanzania/303/2012 Nov A/Alaska/24/2012 Oct # A/Arkansas/05/2012 Dec A/Jiangsu-Danyang/1647/2012 Oct # A/Jiangsu-Donghai/57/2012 Sep # A/Perth/16/2009 # F D93G S315R T148T/I/K (I/K LOSS GLY) D151/D/N/V/G/S/A (N ADD GLY) S367N ADD GLY K369T I464L D127N E258K I307M L338F N342D E381G N402D LOSS GLY R430S E221D T238A V143M L81P N402D LOSS GLY M24T V143M S416N H336N E258K N329T LOSS GLY R150H D251V D304N N43D 3B 3A 5/6 3C A/Perth/16/09- like 1

33. Summary Influenza A(H3N2) viruses caused widespread outbreaks in North America and were the predominant circulating viruses globally. H3N2 viruses also caused regional or widespread activity in some Asian and European countries. The majority of recent A(H3N2) viruses tested were antigenically similar to the cell-propagated A/Victoria/361/2011 reference virus and egg and cell- propagated A/Texas/50/2012 viruses. Post-infection ferret antisera raised against the egg-propagated A/Victoria/361/2011 virus had HI and neutralization titers that were at least 8-fold lower compared to the homologous titer. The HA genes of most recent A(H3N2) viruses fell into phylogenetic clade 3C while a smaller proportion had HA genes that fell into other phylogenetic clades such as 3A, 3B, 5 and 6. These genetic clades were antigenically indistinguishable. All tested H3N2 viruses remained susceptible to neuraminidase inhibitors.

34. Influenza B Viruses Sept 2012 – Jan 2013 Influenza B Viruses Sept 2012 – Jan 2013

35. Introduction In recent years both B/Victoria lineage and B/Yamagata lineage viruses have co-circulated. During the 2012/13 Northern Hemisphere season, the proportion of B/Yamagata lineage viruses increased and this lineage predominated in many countries.

36. Influenza B viruses were 23% of total Data source: FluNet, (www.who.int/flunet), Global Influenza Surveillance and Response System (15 February 2013)www.who.int/flunet

37. Influenza B viruses analyzed by WHO CCs September 2012 to January 2013

38. Influenza B activity Data source: FluNet, (www.who.int/flunet), Global Influenza Surveillance and Response Systemwww.who.int/flunet

39. Number of B Viruses Detected by GISRS Data source: FluNet, (www.who.int/flunet), Global Influenza Surveillance and Response System (15 February 2013)www.who.int/flunet

40. B viruses characterized during the past 3 NH seasons (Sept to Jan)

41. B low reactors in HI assays in WHO CCs WHO CCVictoria (Bris/60/2008) Yamagata (Wisc/1/2010) CDC Low Reactors 119 (80%) 29 (20%) 312 (100%) 0 (0%) CNIC Low Reactors 108 (94%) 7 (6%) 25 (100%) 0 (0%) NIID Low Reactors 19 (100%) 0 (0%) 6 (100%) 0 (0%) NIMR* Low Reactors 26 (97%) 1 (3%) 39 (58%) 28 (42%) (B/Stockholm/12/2011)* VIDRL Low Reactors 163 (93%) 12 (7%) 15 (54%) 13 (46%) Total Low Reactors 435 (90%) 49 (10%) 397 (91%) 41 (9%)

42. B/Victoria Lineage Viruses

43. REFERENCE FERRET ANTISERA Y2Y3V1 MDCKEGGMDCKEGGMDCKEGG MDCKEGGMDCKHADATE REFERENCE ANTIGENSEST/55669MA/02 WI/1W1/1 TX/06BRI/60 NV/03NJ/1GROUPCOLL.PASS. 1B/ESTONIA/55669/2011640320 16032016020555Y-203/14/11C2C2/C2 2B/MASSACHUSETTS/02/2012320 160 20555Y-203/13/12E3 3B/MASSACHUSETTS/02/2012640320640320 105520Y-203/13/12M1/C2 4B/MASSACHUSETTS/02/2012 BX-51B640128032016032016020555REASSE3E7 5B/MASSACHUSETTS/02/2012 BX-51C320640320160 205510REASSE3E7 6B/WISCONSIN/01/201080 40160 805555Y-302/20/10E4 7B/WISCONSIN/01/2010640320160640 32010555Y-302/20/10C1/C2 8B/TEXAS/06/2011160 320 1601055 Y-302/16/11E4 9B/BRISBANE/60/2008*555555128080640160V-1A08/04/08E4/E4 10B/BRISBANE/60/2008555555640160640320V-1A04/08/08CX,C4/C1 11B/NEVADA/03/2011555555320160640320V-1A02/02/11E3 12B/NEW JERSEY/1/2012555555320160640 V-1A04/26/12C2 TEST ANTIGENS 13B/WISCONSIN/15/2012320160640320160 5552012/26/12C1 14B/ARKANSAS/03/2012320160640160 55520Y-212/26/12C1 15B/GEORGIA/01/2013160 320160 5551001/01/13C1 16B/GEORGIA/02/2013320160320160 55510Y-201/04/13C1 17B/NEW MEXICO/04/2012320160640160 55520Y-211/26/12M1/C2 18B/NEW YORK/01/2013160 640160 5552001/10/13C1 19B/OREGON/04/2012160 320160 55510Y-212/31/12M1/C1 20B/TEXAS/24/2012160 640160 55510Y-211/27/12E3 21B/WYOMING/01/2013320160640160 555501/02/13C1 22B/TEXAS/38/2012160 80 5555 12/20/12M1/C1 23B/BANGLADESH/3009/201280 160320160 555509/20/12C2 24B/INDIA/2178/2012160 320160 5551012/20/12C1 25B/INDIA/2239/2012160 320160 5552012/27/12C1 26B/INDIA/2242/2012320160320160 55510 12/28/12C1 27B/TEXAS/37/2012555555320160640 12/24/12C1 28B/UTAH/17/2012555555320160640 V-1A12/25/12C1 29B/NEBRASKA/13/201255555516080640320V-1A12/30/12C1 30B/INDIA/2024/201255555516080320 V-1A11/26/12C1 HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA TYPE B VIRUSES (01/25/13)

44. B/Victoria Antigenic Cartography Recent B/Victoria lineage viruses are antigenically similar to B/Brisbane/60/2008 B/Brisbane/60/2008-cell Sept 2012 to Feb 2013 – Gold, Aug 2011 to Aug 2012 – Blue, Earlier – Grey

45. B/Ohio/01/2005 Feb # LR F B/Hiroshima/09/2010 Sep # LR F cnic A/Jiangsu-Runzhou/1697/2012 Nov # * niid B/Laos/I772/2012 Oct * cnic A/Jiangxi-Xunyang/52/2012 Dec * afrims B/Thailand/KRCH-00010/2012 afrims B/Thailand/PMKA1934/2012 B/Montana/06/2012 Oct LR B/Montana/05/2012 Oct # LR F B/Brisbane/60/2008 Aug F B/Brisbane/60/2008 Aug # F $ B/Michigan/09/2011 Sep # F nimr B/Denmark/23/2012 Nov namru6 B/Peru/IRPc00144/2012 * B/Jiangsu-Hailing/1740/2012 Sep # cnic A/Jiangsu-Qingpu/11269/2012 Oct * B/Nevada/03/2011 Feb # F B/Nevada/03/2011 Feb F B/Uganda/2851/2012 afrims B/Bhutan/BTF-00088/2012 B Victoria HA Consensus 2012-13 usafsam B/Nebraska/1075/2012 Dec usafsam B/Nebraska/908/2012 Dec B/Nebraska/05/2012 Nov cnic A/Jiangsu-Pingjiang/1494/2012 Dec * namru6 B/Nicaragua/INI00520/2012 Nov * afrims B/Philippines/AFPA-00187/2012 B/Louisiana/01/2012 Dec B/Honduras/648/2012 Nov cnic A/Jiangsu-Tianning/1676/2012 Dec # * B/Tanzania/335/2012 Dec LR nimr B/Bayern/1/2013 Jan usafsam B/Florida/1189/2012 Dec usafsam B/Texas/770/2012 Dec B/Peru/1634/2012 Oct namru6 B/Pampagrande/FPT01070/2012 Dec * namru6 B/Piura/FPP01690/2012 Dec * B/Utah/17/2012 Dec usafsam B/Nevada/847/2012 Dec nimr B/Lyon/2760/2012 Dec nimr B/Jordan/30014/2012 Dec afrims B/Thailand/KPPH-00092/2012 B/Bangkok/282/2012 Oct B/Wisconsin/01/2013 Jan LR B/Wyoming/10/2012 Dec B/India/2024/2012 Nov LR cnic A/Fujian-Yanping/2322/2012 Dec * B/Bangladesh/3249/2012 Oct aus B/Victoria/824/2012 Oct usamruk B/Kenya/244/2012 afrims B/Philippines/AFPA-00149/2012 B/Wisconsin/16/2012 Dec LR B/Texas/02/2013 Jan B/Virginia/05/2012 Dec LR B/New Jersey/02/2013 Jan LR Evolutionary Relationships Among Influenza B Victoria Lineage Hemagglutinin (HA) Genes, 2012-13 02/22/2013 LR- Low Reactor to B/Brisbane/60/2008 Egg (≥ 8 fold) F - CDC Reference Antigen $ - CDC Serology Antigen # Egg Isolate * - HA1 region only ____ 165N October 2012 November 2012 December 2012 January 2013 1A 1B Intra-clade Reassortants HA-1A/NA-3 Intra-clade Reassortants HA-1B/NA-4 N75K N165K S172P L58P V87I N129S N171D P58S H122L V15I V146I N218D A169E N129D G184E A154T K209N HA Genetic Groups Since September 2012

46. Evolutionary Relationships Among Influenza B Victoria Lineage Neuraminidase (NA) Genes, 2012-13 02/22/2013 LR- Low Reactor to B/Brisbane/60/2008 Egg (≥ 8 fold) F - CDC Reference Antigen $ - CDC Serology Antigen # Egg Isolate HA Genetic Group Shown October 2012 November 2012 December 2012 January 2013 B/Texas/02/2013 Jan B/Wisconsin/16/2012 Dec LR B/Virginia/05/2012 Dec LR B/New Jersey/02/2013 Jan LR B/Honduras/648/2012 Nov B/Louisiana/01/2012 Dec insert L76 B/Nebraska/05/2012 Nov cnic A/Jiangsu-Pingjiang/1494/2012 Dec cnic A/Jiangsu-Tianning/1676/2012 Dec # nimr B/Lyon/2760/2012 Dec B/Montana/05/2012 Oct # LR F B/Montana/06/2012 Oct LR B/Tanzania/335/2012 Dec LR B/Wisconsin/01/2013 Jan LR B/Wyoming/10/2012 Dec B/Peru/1634/2012 Oct B/Utah/17/2012 Dec nimr B/Bayern/1/2013 Jan B Victoria NA Consensus 2012-13 nimr B/Jordan/30014/2012 Dec B/Bangkok/282/2012 Oct aus B/Victoria/824/2012 Oct B/India/2024/2012 Nov LR B/Bangladesh/3249/2012 Oct cnic A/Fujian-Yanping/2322/2012 Dec B/Uganda/2851/2012 B/Nevada/03/2011 Feb # F B/Nevada/03/2011 Feb F B/Brisbane/60/2008 Aug # F $ B/Brisbane/60/2008 Aug F B/Jiangsu-Hailing/1740/2012 Sep # cnic A/Jiangsu-Qingpu/11269/2012 Oct B/Hiroshima/09/2010 Sep # LR F cnic A/Jiangsu-Runzhou/1697/2012 Nov # B/Ohio/01/2005 Feb # F B/Michigan/09/2011 Sep # F nimr B/Denmark/23/2012 Nov cnic A/Jiangxi-Xunyang/52/2012 Dec S41P P42S N125K V271I K272Q D320K D329E D340N D342G D384N A395V K404E D463N A465T ADD GLY T8M L73F A389T S397R N340D D329N I204V N220K A358E H61Q K375M S295R D35G N59D R65S I348V A395T P51S L73F N199D V63M K343E L73F N198S S345N 1A 1B Intra-clade Reassortants HA-1A/NA-3 3 Intra-clade Reassortants HA-1B/NA-4 4

47. B/Yamagata Lineage Viruses WHO information meeting on influenza vaccine composition for southern hemisphere 2013 20 September 2012 Beijing

48. Antigenic analysis of B/Yamagata viruses (1)

49. Antigenic analysis of B/Yamagata viruses (2)

50. REFERENCE FERRET ANTISERA Y1Y2Y3 EGGMDCKEGGMDCKEGGMDCKHADATE FL/4EST/55669MA/02 WI/1W1/1 TX/06 GROUPCOLL.PASS. 1B/FLORIDA/04/200651201280 320640320640Y-111/01/06E3 2B/ESTONIA/55669/20111280640320 160320160320Y-203/14/11C2C2/C2 3B/MASSACHUSETTS/02/2012640320 160 Y-203/13/12E3 4B/MASSACHUSETTS/02/20121280640320640320 Y-203/13/12M1/C2 5B/MASSACHUSETTS/02/2012 BX-51B25606401280320160320160320REASSE3E7 6B/MASSACHUSETTS/02/2012 BX-51C2560320640320160 REASSE3E7 7B/WISCONSIN/01/201032080 40160 80160Y-302/20/10E4 8B/WISCONSIN/01/20101280640320160640 320640Y-302/20/10C1/C2 9B/TEXAS/06/2011640160 320 160320Y-302/16/11E4 10B/TEXAS/06/2011320160 320 640Y-302/16/11M1/C2 TEST ANTIGENS 11B/WISCONSIN/15/2012320 160640320160 32012/26/12C1 12B/ARKANSAS/03/2012320 160640160 320Y-212/26/12C1 13B/GEORGIA/01/2013320160 320160 32001/01/13C1 14B/GEORGIA/02/2013320 160320160 320Y-201/04/13C1 15B/NEW MEXICO/04/2012320 160640160 320Y-211/26/12M1/C2 16B/NEW YORK/01/2013320160 640160 32001/10/13C1 17B/OREGON/04/2012320160 320160 320Y-212/31/12M1/C1 18B/TEXAS/24/2012320160 640160 Y-211/27/12E3 19B/WYOMING/01/2013640320160640160 32001/02/13C1 20B/TEXAS/38/2012320160 80 160 12/20/12M1/C1 21B/BANGLADESH/3009/201216080 160320160 32009/20/12C2 22B/INDIA/2178/2012320160 320160 12/20/12C1 23B/INDIA/2239/2012320160 320160 32012/27/12C1 24B/INDIA/2242/2012640320160320160 320 12/28/12C1 HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA B/YAMAGATA-LINEAGE VIRUSES (01/25/13)

51. B/Yamagata Antigenic Cartography Clade 2 and 3 viruses were antigenically distinguishable by many sera B/Wisconsin/1/2010-egg Sept 2012 to Feb 2013 – Gold, Aug 2011 to Aug 2012 – Blue, Earlier – Grey B/Massachusetts/2/2012-egg

52. B/Florida/04/2006 Nov # F B/Wisconsin/01/2010 Feb F $ B/Wisconsin/01/2010 Feb # F $ B/Bangladesh/7005/2012 Oct B/Hawaii/13/2012 Nov cnic B/Heilongjiang-Jiguan/1409/2012 Dec * B/Nong Khai/322/2012 Oct B/Hubei-Wujiagang/158/2009 Mar # F B/Vermont/07/2012 Dec nimr B/Rheinland-Pfalz/4/2013 Jan usafsam B/Nevada/845/2012 Dec B/Texas/06/2011 Feb F B/Texas/06/2011 Feb # F B/Cote DIvoire/1507/2012 Dec nimr B/Ghana/DILI-0859/2012 Oct B/Quebec/RV2958/2012 Nov B/Dominican Republic/6986/2012 Dec aus B/Brisbane/36/2012 Jun B/Estonia/55669/2011 Mar F afrims B/Thailand/KPPH-00148/2012 B/Massachusetts/02/2012 Mar F $ aus B/Wellington/3/2012 Jul B/Nevada/17/2012 Dec B/Massachusetts/02/2012 BX-51C # F B/Massachusetts/02/2012 Mar # F $ B/Massachusetts/02/2012 BX-51B F B/Alabama/01/2013 Jan B/Chanthaburi/318/2012 Oct niid B/Yokohama/82/2012 Dec * B/Texas/24/2012 Nov # usafsam A/Oklahoma/1557/2013 Jan afrims B/Bhutan/BTG-00006/2012 usafsam B/Texas/1322/2013 Jan usafsam B/Colorado/1468/2013 Jan lrmc B/Germany/x170/2013 Jan B/North Carolina/05/2012 Dec B/New Mexico/04/2012 Nov $ nimr B/Lyon/2771/2012 Dec B/India/2127/2012 Dec B/Kansas/02/2012 Dec B/Missouri/01/2013 Jan usafsam B/Alaska/1351/2012 Dec usafsam B/Illinois/704/2012 Dec B/Oman/14/2013 Jan usafsam B/SouthCarolina/1462/2013 Jan B Yamagata HA Consensus 2012-13 usafsam B/NewYork/1201/2013 Jan B/India/2152/2012 Dec lrmc B/Belgium/x54/2012 B/Texas/01/2013 Jan usafsam B/Florida/1376/2013 Jan B/Ohio/01/2013 Jan usafsam B/Maryland/583/2012 Dec B/Georgia/02/2013 Jan B/Georgia/04/2013 Jan Evolutionary Relationships Among Influenza B Yamagata Lineage Hemagglutinin (HA) Genes, 2012-13 Y2 Y3 HA Genetic Groups Since September 2012 K88R E479D R48K P108A T182A S230G S150I N166Y S230D T182K N203S M252V V29A L173Q K299E E313K T37A K299E E313K N116K T189A N197D LOSS GLY

53. Evolutionary Relationships Among Influenza B Yamagata Lineage Neuraminidase (NA) Genes, 2012-13 B/New Mexico/04/2012 Nov $ B/Ohio/01/2013 Jan B/Texas/01/2013 Jan B/Georgia/02/2013 Jan B/Georgia/04/2013 Jan B/Kansas/02/2012 Dec B Yamagata NA Consensus 2012-13 B/India/2127/2012 Dec niid B/Yokohama/82/2012 Dec nimr B/Lyon/2771/2012 Dec B/India/2152/2012 Dec B/Chanthaburi/318/2012 Oct B/North Carolina/05/2012 Dec B/Oman/14/2013 Jan B/Estonia/55669/2011 Mar F aus B/Wellington/3/2012 Jul B/Nevada/17/2012 Dec B/Massachusetts/02/2012 BX-51B F B/Massachusetts/02/2012 BX-51C F B/Massachusetts/02/2012 Mar # F $ B/Massachusetts/02/2012 Mar F $ aus B/Brisbane/36/2012 Jun B/Cote DIvoire/1507/2012 Dec nimr B/Ghana/DILI-0859/2012 Oct B/Quebec/RV2958/2012 Nov B/Dominican Republic/6986/2012 Dec B/Texas/06/2011 Feb # F B/Texas/06/2011 Feb F B/Vermont/07/2012 Dec nimr B/Rheinland-Pfalz/4/2013 Jan B/Hubei-Wujiagang/158/2009 Mar # F B/Wisconsin/01/2010 Feb # F $ B/Wisconsin/01/2010 Feb F $ B/Hawaii/13/2012 Nov B/Bangladesh/7005/2012 Oct B/Nong Khai/322/2012 Oct cnic B/Heilongjiang-Jiguan/1409/2012 Dec B/Florida/04/2006 Nov # F Y2 Y3 D463N A465T ADD GLY Q42R A68T T125K K186R D340N T106I I248V S295R A55T R65H L73P K343E

54. Summary B/Victoria and B/Yamagata lineage viruses co-circulated. The proportion of B/Yamagata viruses has increased in many countries, while B/Victoria viruses predominated in some countries. B/Victoria lineage viruses –Antigenically and genetically remain similar to the previously used vaccine virus, B/Brisbane/60/2008. B/Yamagata lineage viruses – HA genes of the viruses were in clade 2 or 3. –Clade 3 viruses were antigenically and genetically closely related to the 2012/13 NH vaccine virus, B/Wisconsin/1/2010. –Some ferret antisera are able to detect antigenic differences between recent clade 2 and 3 viruses. –Clade 2 viruses have circulated widely in recent months.

55. Summary of A(H1N1)pdm09 viruses A(H1N1)pdm09 viruses Continued to circulate at relatively low levels Increase observed in some parts of Europe in January Viruses are antigenically similar to A/California/7/2009 vaccine virus HA genes are in clades 6 and 7 but these clades are antigentically indistinguishable.

56. Summary of influenza A(H3N2) Predominant viruses globally and especially in Canada and the U.S. Some other countries in the Northern Hemisphere reported regional and widespread outbreaks. Most recent viruses have HAs that: –Genetically fall into clade 3C; remainder fall into clades 3A, 3B, 5 and 6 –Antigenically indistinguishable –Antigenically similar to cell-propagated A/Victoria/361/2011, egg- and cell- propagated A/Texas/50/2012 viruses –Showed at least 8-fold reduction in HI and NT using antisera against egg- propagated A/Victoria/361/2011

57. Summary of influenza B (1) Influenza B viruses circulated and caused outbreaks in many countries. Both B/Victoria/2/87 and B/Yamagata/16/88 lineages co-circulated. –B-Vic viruses prevalent in some countries (e.g., China) –B-Yam viruses continued to increase in proportion and becoming dominant in many countries The majority of recent B/Victoria/2/87 lineage viruses were antigenically and genetically closely related to B/Brisbane/60/2008. Most recent B/Yamagata/16/88 lineage viruses –HA genes fall into clades 2 or 3, with the proportion of clade 2 viruses increasing significantly in Europe and North America –Many clade 2 vs. clade 3 viruses are antigenically distinguishable in HI tests especially in laboratories in Melbourne and London

58. Publications Vaccine composition recommendation report and summary report on H5/H9 vaccine viruses: –WHO GlSRS website: http://www.who.int/influenza/gisrs_laboratory/en/ http://www.who.int/influenza/vaccines/virus/en/ –WHO Weekly Epidemiological Record: http://www.who.int/wer/en/ Candidate vaccine viruses and reagents –http://www.who.int/influenza/vaccines/virus/en/http://www.who.int/influenza/vaccines/virus/en/ WHO Global Influenza Surveillance and Response System (GISRS): GISRS-WHOHQ@who.int

59. Acknowledgements WHO Collaborating Centers in Beijing, London, Melbourne and Tokyo for seasonal influenza data National Influenza Centers (over 20 submitted written reports in addition to data provided through FluNet) Essential Regulatory Laboratories for human serology data Many staff from CDC’s Influenza Division, including Alexander (Sasha) Klimov, Xiyan Xu, Rebecca Garten, Julie Villanueva, Angie Foust, Wendy Sessions, Elizabeth Blanchard, Thomas Rowe, Jan Mabry, Jackie Katz, Vic Vegilla and many others