Overview of Influenza Activity and Characterizations of Viruses isolated in 2011/12 season in Northern Hemisphere

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1 6thMeeting of NICs in the WPR and SEAR May, 2012 Hanoi VN Overview of Influenza Activity and Characterizations of Viruses isolated in 2011/12 season in Northern Hemisphere Takato Odagiri WHO Collaborating Center for References and Researchon Influenza, National Institute of Infectious Diseases, Tokyo, Japan

2 Influenza Activity in 2011/12 season (Northern Hemi.) As of May 9, 2012 B H3N2 H1N1pdm09 As of Feb, 2012 B(not determined), 9837, 27% A(H1N1)pdm09, 6223, 17% B(Victoria), 1465, 4% B(Yamagata), 758, 2% A(not subtyped), 3830, 10% A(H3), 14713, 40%

3 Influenza Activity in 2011/12 season (WHO CCs Tokyo & Atlanta) As of May 9, 2012 Vic : Yama = 2:1 H3N2 B H3 75% B 25% H1N1pdm09 H3N2 B

4 Influenza Activity in 2011/12 season (W14, 2011 W19, 2012) (WHO CC, China) Number of Positive Untyped Yamagata Victoria B(lineage not determined) A(unsubtyped) H1N1 H3N2 H1N1pdm Influenza Positive(%) B/Yama B/Vic South China H3N Percent positive Week Number of Positive Untyped Yamagata Victoria B(lineage not determined) A(unsubtyped) H1N1 H3N2 H1N1pdm Influenza Positive(%) North China B/Yama B/Vic H3N2 H1N1pdm Percent positive Week

5 Detection of NAIs-Resistant Viruses in 2011/12 season (as of Feb, 2012) WHO CCs H1N1pdm09 H3N2 B Osel/Perami Zanami Osel/Perami Zanami Osel/Perami Zanami US-CDC 1/122 (1.5%) 0/115 0/357 0/357 0/175 0/175 NIMR 0/89 0/89 0/250 0/250 3/127 (2.4%) 3/127 (2.4%) China-CDC - - 0/97-1/374 (0.3%) - NIID 0/1 0/1 0/97 0/97 0/23 0/23 Melbourne 8/508 (1.6%) 0/508 0/503 0/503 0/648 0/648

6 A(H1N1)pdm09 viruses

7

8

9 Antigenic cartography of A(H1N1)pdm09 viruses Since 2009 Since August 2011

10

11 A(H3N2) viruses

12

13 2010/11 season (as of Feb, 2011) 2011/12 season (as of April, 2012) Brisbane/299/11 5, 6 3 Victoria/361/11 Globally Victoria/210/09 Perth/16/09 vaccine Victoria/210/09 Perth/16/09

14 H3 HA gene evolution

15

16 H3 low reactors in HI assays in WHO CCs WHO CC A/Perth/16/09 Low ( 8 fold) CDC 469 (90%) 49 (10%) CNIC 36 (92%) 3 (8%) NIID 41 (100%) 0 (0%) NIMR 61 (67%) 30 (33%) VIDRL 274 (99%) 3 (1%) Total 801 (89%) 85 (11%)

17 Antigenic Cartography: HI Data from NIMR Summary 3A 3B 5 6 Victoria/210/0 9 Perth/16/09 Victoria/210/0 9 Perth/16/09

18 Hemagglutination inhibition tests of influenza A/H3 viruses Strains Passage History Sample date Postinfection Ferret antira Perth16 group Victoria208 group CL1 CL3 CL6 Niigata/ Victoria/ Victoria/ Brisbane/ 403/09 361/11 361/11 299/11 Cell Cell Egg Cell Victoria/ 210/09 Egg Brisbane/ 299/11 Egg Reference Antigens A/Victoria/210/2009 E /06/ A/NIIGATA/403/2009 MDCK /03/ A/Victoria/361/2011 MDCK A/Victoria/361/2011 E A/Brisbane/299/2011 MDCK A/Brisbane/299/2011 E Test Antigens A/SAPPORO/50/2012 MDCK /02/ A/GIFU/20/2012 MDCK /01/ A/GIFU/21/2012 MDCK /01/ A/AKITA/57/2011 MDCK /11/ A/YAMAGATA/127/2012 MDCK /02/ A/WAKAYAMA/102/2012 MDCK /01/ A/HOKKAIDO/1/2012 MDCK /01/ A/HOKKAIDO/26/2012 MDCK /02/ A/HYOGO/1204/2012 MDCK /01/ A/GUNMA/38/2012 MDCK /01/ A/SHIZUOKA/28/2012 MDCK /02/ A/CHIBA/1067/2011 MDCK /12/ A/YAMAGATA/116/2012 MDCK /02/ A/IBARAKI/194/2011 MDCK /12/ A/IBARAKI/6/2012 MDCK /01/ A/OSAKA-C/18/2011 MDCK /12/

19 Comparison of reactivities of antisera elicited by cell- and egg-grown A/Victoria/361/2011 viruses Antisera to Cell-grown wt US-CDC WHO-Mel NIID 100% 100% 97% N=53 N=18 N=30 3% Egg-grown wt 7% 3% 3% 28% 21% 31% 100% 63% 44% N=481 N=36 N=62 Like (<2-fold) 4-fold low 8-fold low >16-fold low

20 Amino acid differences in the HA protein of cell- and egg-grown A/Victoria/361/2011 viruses Amino acid position passage (SITE: B) Viruses history Number of A.A. differences A/Victoria/361/2011 C2/C2 H G - A/Victoria/361/2011 E3+1 R V SITE: B SITE: B SITE: D 219 SITE: D top Green: A/Victoria/361/2011 (cell-grown) Red: A/Victoria/361/2011 (egg-grown) side

21 Comparison of reactivities of antisera elicited by cell- and egg-grown A/Brisbane/299/2011 viruses Antisera to US-CDC WHO-Mel NIID Cell-grown wt N=575 N=68 N=32 Egg-grown wt N=186 N=68 N=32 Like (<2-fold) 4-fold low 8-fold low >16-fold low

22 Amino acid differences in the HA protein of cell- and egg-grown A/Brisbane/299/2011 viruses Amino acid position passage (SITE: B) Viruses history Number of A.A. differences A/Brisbane/299/2011 CK4+2 A H G D S N - A/Brisbane/299/2011 E5+1 S/A H/L D/G D/G S/F N/T SITE: B SITE: A SITE: D SITE: B SITE: D SITE: A top Green: A/Brisbane/299/2011 (cell-grown) Red: A/Brisbane/299/2011 (egg-grown) 290 side

23 Influenza B viruses

24 B/Yamagata and B/Victoria isolations B/Victoria Blue, B/Yamagata- Red from August 2011

25 B/Victoria lineage viruses Phylogenetic analysis of HA gene sequences.

26 Hemagglutination inhibition tests of influenza B viruses (Victoria lineage)-0.5%crbcs Strains Passage History Sample date Brisbane/ 60/08 Cell Clade 1 Clade 4 Clade 5 Sakai/ Brisbane/ 43/08 FujianGulou/ Taiwan/ 60/08 Cell 1272/08 55/09 Cell Egg Boosted Egg Rabbit serum REF.Ag B/Brisbane/60/2008 MDCKx/ /08/ B/Brisbane/60/2008 E /08/ B/SAKAI/43/2008 MDCK /11/ B/Fujian Gulou/1272/2008 E1/E /03/ B/Taiwan/55/2009 MDCK /11/ TEST.Ag B/HYOGO/1119/2011 MDCK /12/ B/GUNMA/5/2012 MDCK /01/ B/NIIGATA/138/2012 MDCK /01/ B/IBARAKI/3/2012 MDCK /01/ B/OSAKA-C/1035/2011 MDCK /12/ B/FUKUI/2/2012 MDCK /01/ B/NIIGATA/163/2012 MDCK /01/ B/GUNMA/7/2012 MDCK /01/ B/Jiangsu-Runzhou/1647/2011 C /11/ B/Jiangsu-Jurong/1652/2011 C /11/ B/Jiangsu-Tinghu/1462/2011 C /11/ B/OKAYAMA/1/2012 MDCK /01/ B/Shanghai-Zhabei/1298/2011 C /11/ B/Shanghai-Minhang/1655/2011 C /11/ B/YAMAGUCHI/2/2012 MDCK /01/ B/Hunan-Yueyanglou/58/2011 C /11/ B/Shanghai-Chongming/1461/2011 C /11/

27 Influenza B/Victoria lineage antigenic cartography Brisbane/60 Cell grown Brisbane/60 Egg grown

28 Amino acid differences in the HA protein of cell- and egg-grown B/Brisbane/60/2008 viruses B/Brisbane/60/2008 E4/E4 : Egg grown virus 197S N-linked glycan B/Brisbane/60/2008 MDCKx/1 : MDCK Cell grown virus 197N Receptor-binding site

29 Florida/4/06 B/Yamagata lineage viruses Phylogenetic analysis of HA gene sequences. Wis/1/10

30 REF.Ag Strains Hemagglutination inhibition tests of influenza B viruses (Yamagata lineage)-0.5%crbcs by NIID Passage History Sample date Florida/ 04/06 Egg No.08-1 Bangladesh/ 3333/07 Egg No.2 Wisconsin/ 1/10 Egg No.2 Sakai/68/09 Cell No.1 B/Florida/04/2006 E2 /E /12/ B/Bangladesh/3333/2007 E /08/ B/Wisconsin/01/2010 E N196N/D B/SAKAI/68/2009 MDCK /11/ TEST.Ag B/SAKAI/36/2011 MDCK /11/ B/HIROSHIMA/64/2011 MDCK /11/ B/KANAGAWA/37/2011 MDCK /10/ B/Taiwan/1124/2011 MDCK /11/ B/SAKAI/31/2011 MDCK /09/ B/TOKYO/11858/2011 MDCK /10/ B/Taiwan/1091/2011 MDCK /11/ B/Taiwan/1241/2011 MDCK /11/ Remarks Strains Hemagglutination inhibition tests of influenza B/Yamagata-lineage viruses by NIMR Passage History Sample date B/FL/4/06 Egg F20/07 B/Bang/3333/07 Egg F24/10 B/Wis/1/10 Egg F26/10 B/Serbia/1894/11 Cell F25/11 REF.Ag B/Florida/4/2006 E3/E4 2006/12/ B/Bangladesh/3333/2007 E3/E4 2007/8/ B/Wisconsin/1/2010 E3/E2 2010/2/ B/Seribia/1894/2011 MDCK1/MDCK4 2011/3/ TEST.Ag B/Texas/06/2011 E4/E2 2011/2/ < B/Adjame/GR874/2011 MDCK /9/ B/Adjame/GR877/2011 MDCK /9/ B/Adjame/GR890/2011 MDCK /9/ B/Yopougon/GR882/2011 MDCK /9/ B/Yopougon/GR926/2011 MDCK /9/ B/Hong Kong/1127/2011 MDCK2/MDCK1 2011/10/ B/Attecoube/GR1101/2011 MDCK /01/ B/Catalonia/S4125/2011 MDCK /11/ B/Hong Kong/1121/2011 MDCK2/MDCK1 2011/12/ B/Catalonia/S4151/2011 MDCK /12/

31 Amino acid differences in the HA protein of cell- and egg-grown B/Wisconsin/01/2010 viruses Viruses passage history 196 B/Wisconsin/01/2010 C1/C2 N B/Wisconsin/01/2010 E3+3 D Glycan 196N 196D Green: B/Wisconsin/01/2010 (cell-grown) Red: B/Wisconsin/01/2010 (egg-grown) Receptor binding pocket

32 Summary of WHO CC antigenic results Total 2-fold 4-fold 8-fold WHO CC assayed B/Victoria Lineage B/Brisbane/60/ (88.9%) 2 (11.1%) 0 London Post-infection ferret (83.8%) 20 (13.5%) 4 (2.7%) Atlanta serum (80.5%) (19.5%) Beijing (70.3%) 26 (28.6%) 1 (1.1%) Melbourne Tokyo B/Yamagata Lineage B/Wisconsin/01/ (43.3%) 8 (26.7%) 9 (30.0%) London Post-infection ferret Atlanta serum (95.8%) 0 8 (4.2%) Beijing (95%) 0 1 (5.0%) Melbourne (82.1%) 4 (10.3%) 3 (7.6%) Tokyo

33 Antibody prevalence of Japanese individuals against influenza B viruses Victoria-lineage (B/Brisbane/60) Yamagata-lineage (B/Wisconsin/1) N= 7049 N= 7049 Reactivity of post-vaccination serum antibodies against epidemic B viruses

34 Recommendation It is recommended that the following viruses be used for influenza vaccines in the influenza season (northern hemisphere): an A/California/7/2009 (H1N1)pdm09-like virus; an A/Victoria/361/2011 (H3N2)-like virus; and a B/Wisconsin/1/2010-like virus (Yamagata-lineage).

35 Acknowledgement All National Influenza Centers of GISRS WHO Collaborating Centers for Reference and Research on Influenza

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