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INFORMATION FOR THE VACCINE AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE CBER, FDA

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,

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INFORMATION FOR THE VACCINE AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE CBER, FDA

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  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 reviewand 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 2013maximum 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)

  5. Susceptibility to Neuraminidase Inhibitors: Inhibition of Neuraminidase Activitya • Virus collection period: Oct 01, 2012 - Jan 21, 2013 a Viruses were tested in the fluorescent NA inhibition assay. Inhibition is based on fold difference in IC50 of a test virus compared to the median IC50 value for type/subtype. The WHO AVWG criteria: Type A viruses - Normal: <10-fold; Reduced: 10-100-fold; Highly reduced: >100-fold.Type B viruses - Normal: <5-fold; Reduced: 5-50-fold; Highly reduced: >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.

  6. A(H1N1)pdm09 VirusesSept 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)

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

  9. (H1N1)pdm09 low reactors in HI assays by WHO CCs

  10. HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA A(H1N1)pdm09 VIRUSES (01/23/13)

  11. HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA A(H1N1)pdm09 VIRUSES (01/29/13)

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

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

  14. 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 N44S ADD GLY A/Ohio/02/2013 Jan N222D L40V A/California/09/2013 Jan 7 I106V N200S 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 V241I N369K 6 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 $ G41R N44S ADD GLY A/Washington/24/2012 Jun @ F 7 A/Wyoming/31/2012 Dec @ V106I A/Japan/1419/2013 Jan N248D 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 @ N386S LOSS GLY 6 nimr A/Netherlands/507/2012 Aug @ cnic A/Jilin-Chaoyang/SWL1709/2012 Dec D451G 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 5 A/Nigeria/7781/2012 Oct F74V N385T A/Cote DIvoire/1575/2013 Jan 8 N386K LOSS GLY 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 #

  15. 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. Summary - 1

  16. Summary - 2 • 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.

  17. A(H3N2)VirusesSept 2012 – Jan 2013

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

  19. H3N2 Viruses Characterized During the Past 3 Years from September to January USA China Japan UK Australia

  20. H3 low reactors in HI assays by WHO CCs

  21. 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.

  22. Antigenic Analysis of Influenza A(H3N2) Viruses - Plaque Reduction Neutralization(MDCK-SIAT)

  23. Summary of fold differences between reference viruses and test antigens in HI assays performed by CDC since January 2013

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

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

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

  27. H3N2 Hemagglutinin changes compared toA/Victoria/361/2011- cell G186V I226S

  28. Evolutionary Relationships Among Influenza A (H3N2) Hemagglutinin (HA) Genes, 2012-13 02/22/2013 Current Northern Hemisphere Vaccine Strain WHO Recommendation 2013-2014 LR- Low Reactor to A/Victoria/361/2011 cell (≥ 8 fold) F - CDC Reference Antigen $- CDC Serology Antigen C$- Common Serology Antigen # Egg Isolate * – only HA1 region October 2012 November 2012 December 2012 January 2013 A/North Carolina/01/2013 Jan A/Oklahoma/03/2013 Jan usafsam A/Georgia/1407/2013 Jan A/Beijing-Xicheng/12423/2012 Oct $ lrmc A/Qatar/x119/2013 Jan T128A LOSS GLY R142G A/West Virginia/01/2013 Jan A/New York/39/2012 Oct # usafsam A/NewYork/1365/2013 Jan 3C.3 A/Yamaguchi/30/2012 Oct LR A/Rhode Island/02/2013 Jan nimr A/Athens GR/14/2013 Jan A/Virginia/03/2013 Jan cnic A/Beijing-Huairou/128/2013 Jan * A/Nebraska/02/2013 Jan R33Q A/Oregon/15/2012 Dec A/Colorado/27/2012 Dec usafsam A/Alabama/1197/2013 Jan usafsam A/SouthDakota/1410/2013 Jan A/Montana/01/2013 Jan nimr A/England/676/2012 Dec A/North Dakota/08/2012 Dec A/New York/03/2013 Jan usafsam A/Virginia/1373/2013 Jan A/South Dakota/12/2012 Oct # A/Ohio/01/2013 Jan D489N nhrc A/Illinois/NHRC367623/2012 Dec * 3C usafsam A/DistrictofColombia/1414/2013 Jan A/Illinois/01/2013 Jan lrmc A/Italy/x178/2013 Jan usafsam A/Guam/1490/2012 Dec N145S usafsam A/Florida/1324/2013 Jan 3C.2 nimr A/Sachsen/2/2013 Jan cnic A/Heilongjiang-Xiangfang/11272/2012 Dec * A/Ontario/RV2944/2012 Nov A/North Carolina/02/2013 Jan namru2 A/Cambodia/FSS22141/2013 Nov usafsam A/Washington/1531/2013 Jan A/California/04/2013 Jan Q33R N278K A/Arizona/09/2012 Oct # F niid A/Yokohama/164/2012 Dec * A/Delaware/15/2012 Nov F $ A/Delaware/01/2013 Jan LR S45N ADD GLY T48I A/Seoul/3531/2012 Dec A H3 HA Consensus 2012-13 A/Texas/50/2012 X-223 # F I226N T128N LOSS GLY A198P G186V S219F A/Texas/50/2012 X-223A # F A/Texas/50/2012 Apr # F $ A/Texas/50/2012 Apr F $ H156Q G186V S219Y 3C.1 A198S N312S A/Hawaii/22/2012 Jul # F A/Hawaii/22/2012 Jul F $ A/Victoria/361/2011 Oct # F $ N144K LOSS GLY A/Victoria/361/2011 IVR-165 # F A/Victoria/361/2011 Oct F $ nimr A/Cairo/136/2012 Dec nimr A/Ukraine/551/2012 Dec V223I 3B namru2 A/Cambodia/FSS23444/2012 Nov K62E K144N ADD GLY T212A N145S D487N A/Ohio/02/2012 X-221 # F A/Ohio/02/2012 Mar # F N144D LOSS GLY N145S D487N A/Ohio/02/2012 Mar F L3I D53N A/Alaska/24/2012 Oct # 3A HA Genetic Groups Since September 2012 A/Arkansas/05/2012 Dec A/Tanzania/303/2012 Nov usafsam A/Texas/1406/2013 Jan K2E A/Florida/01/2013 Jan D53N Y94H I230V E280A 5 N8D LOSS GLY A/South Carolina/16/2012 Nov $ A/Delaware/23/2012 Dec # nimr A/Austria/710638/2012 Dec usafsam A/Florida/1378/2013 Jan A/Brisbane/299/2011 Aug # F P162S I260M R261Q 6 A/Virginia/16/2012 Dec # S199A A/Puerto Rico/36/2012 Jun # F A/Perth/16/09-like 1 A/Jiangsu-Donghai/57/2012 Sep # A/Jiangsu-Danyang/1647/2012 Oct # A/Perth/16/2009 # F

  29. Evolutionary Relationships Among Influenza A (H3N2) Neuraminidase (NA) Genes, 2012-13 N43D 02/22/2013 Current Northern Hemisphere Vaccine Strain WHO Recommendation 2013-2014 LR- Low Reactor to A/Victoria/361/2011 cell (≥ 8 fold) F - CDC Reference Antigen $- CDC Serology Antigen C$- Common Serology Antigen # Egg Isolate HA Genetic Group Shown October 2012 November 2012 December 2012 January 2013 A/New York/39/2012 Oct # A/West Virginia/01/2013 Jan A/Rhode Island/02/2013 Jan A/Virginia/03/2013 Jan M24T 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 V143M A/Ohio/01/2013 Jan A/Illinois/01/2013 Jan A/Yamaguchi/30/2012 Oct LR A/Delaware/15/2012 Nov F $ 3C 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 Apr F $ D93G A/Texas/50/2012 X-223A # F A/Texas/50/2012 X-223 # F R150H A/Victoria/361/2011 IVR-165 # F E258K N329T LOSS GLY A/Victoria/361/2011 Oct # F $ A/Victoria/361/2011 Oct F $ L81P N402D LOSS GLY A/Ohio/02/2012 Mar # F D251V D304N 3B A/Ohio/02/2012 Mar F $ nimr A/Cairo/136/2012 Dec nimr A/Ukraine/551/2012 Dec S367N ADD GLY K369T I464L A/South Carolina/22/2012 Nov A/Virginia/16/2012 Dec # A/Puerto Rico/36/2012 Jun # F nimr A/Austria/710638/2012 Dec 5/6 S315R T148T/I/K (I/K LOSS GLY) D151/D/N/V/G/S/A (N ADD GLY) A/Delaware/23/2012 Dec # A/Florida/01/2013 Jan V143M A/South Carolina/16/2012 Nov $ A/Brisbane/299/2011 Aug # F A/Tanzania/303/2012 Nov S416N E221D T238A 3A A/Alaska/24/2012 Oct # H336N A/Arkansas/05/2012 Dec D127N E258K I307M L338F N342D E381G N402D LOSS GLY R430S A/Perth/16/09-like 1 A/Jiangsu-Danyang/1647/2012 Oct # A/Jiangsu-Donghai/57/2012 Sep # A/Perth/16/2009 # F

  30. 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.

  31. Influenza B Viruses Sept 2012 – Jan 2013

  32. 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.

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

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

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

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

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

  38. B low reactors in HI assays in WHO CCs

  39. B/Victoria Lineage Viruses

  40. HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA TYPE B VIRUSES (01/25/13)

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

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

  43. 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 1B B/Montana/05/2012 Oct # LR F L73F B/Montana/06/2012 Oct LR B/Tanzania/335/2012 Dec LR B/Wisconsin/01/2013 Jan LR B/Wyoming/10/2012 Dec 1A B/Peru/1634/2012 Oct B/Utah/17/2012 Dec L73F S295R nimr B/Bayern/1/2013 Jan B Victoria NA Consensus 2012-13 nimr B/Jordan/30014/2012 Dec N198S S345N B/Bangkok/282/2012 Oct aus B/Victoria/824/2012 Oct N340D B/India/2024/2012 Nov LR B/Bangladesh/3249/2012 Oct K343E cnic A/Fujian-Yanping/2322/2012 Dec B/Uganda/2851/2012 B/Nevada/03/2011 Feb # F V63M B/Nevada/03/2011 Feb F D329N B/Brisbane/60/2008 Aug # F $ I204V N220K A358E B/Brisbane/60/2008 Aug F B/Jiangsu-Hailing/1740/2012 Sep # H61Q K375M D35G N59D R65S I348V A395T cnic A/Jiangsu-Qingpu/11269/2012 Oct P51S L73F N199D 1B B/Hiroshima/09/2010 Sep # LR F cnic A/Jiangsu-Runzhou/1697/2012 Nov # Intra-clade Reassortants HA-1A/NA-3 B/Ohio/01/2005 Feb # F 3 B/Michigan/09/2011 Sep # F T8M L73F A389T S397R nimr B/Denmark/23/2012 Nov 4 Intra-clade Reassortants HA-1B/NA-4 S41P P42S N125K V271I K272Q D320K D329E D340N D342G cnic A/Jiangxi-Xunyang/52/2012 Dec D384N A395V K404E D463N A465T ADD GLY

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

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

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

  47. HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA B/YAMAGATA-LINEAGE VIRUSES (01/25/13)

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