1. Influenza Activity and Virus Characterizations (Northern Hemisphere) 5thMeeting of NICs in the WPR and SEAR 7-10 June, 2011 Laos Takato Odagiri WHO Collaborating Center for References and Research on Influenza, National Institute of Infectious Diseases, Tokyo, Japan

2. Influenza subtypes 2010- 2011: Northern Hemisphere (as of May 23,2011) B H1N1pdm09 H3N2 WHO, FluNet

3. A(H5N1), 14 viruses - Cambodia (1) ： CL 1 - Hong Kong (1) ： CL2.3.2 - Egypt (10) ： CL 2.2.1 - Indonesia (2) ： CL 2.1.2 Percentage of influenza viruses by subtypes (From 29 August 2010 – 29 January 2011) 31% 27% 21% WHO, FluNet

5. 54% 32%14% 98% 2%2% 0%0%

6. Antigenic and genetic characterizations A(H1N1)pdm09 viruses

8. Antigenic analysis of A (H1N1)pdm09 viruses by HI tests Mar –Aug, 2010 JPN, China, Taiwan, Korea, Mongol, Laos, Myanmar, Singapore JPN, China, Taiwan, Korea, Mongol, Laos, Myanmar, Singapore N+C America, EU, Asia, Africa, AU, NZ N+C America, EU, Asia, Africa, AU, NZ NIID CDC =4-fold low >8-fold low 2%2% 2%2% 1% Sept, 2010 –Feb, 2011 A/Cal-like =4-fold low 1% 99% A/Cal-like 94% =4-fold low 6%6% 6%6% A/Cal-like 89% =4-fold low 9%9% 9%9% >8-fold low 2%2% 2%2% 95% A/Cal-like 83% >8-fold low 2%2% 2%2% A/Cal-like 99% NIMR EU, Africa >8-fold low 1% A/Cal-like 100% C-CDC China >8-fold low 2%2% 2%2% A/Cal-like 98%

9. Antigenic cartography of A(H1N1)pdm09 isolates (Cambridge University) Antigenic cartography of A(H1N1)pdm09 isolates (Cambridge University) Vast majority of A(H1N1)pdm09 viruses remained antigenically homologous to the A/California/07/2009 vaccine virus. A/California/07/2009

10. Amino acid substitutions in H1N1pdm-HA protein that result in antigenic change from A/Cal/7/2009 Position 155 G to E Position 155 G to E Position 156 N to D Position 156 N to D Position 157 S to L Position 157 S to L Colin, Derek et al, Cambridge U.

11. 外 2010/11 Early phase (2010. Sept to 2011. Jan ） 2009/10 late phase (2010, April to July ） Majority clade Vaccine strain

12. 3 1 2 5 2 6 7 1 2 3 2 1 1 1 2 5 1 1 1 1 6 1 2 2 1 1 275Y 1.9% (53/2761) 275H/Y 0.3% (8/2761) China -CDC NIID Detection of Antiviral resistant H1N1pdm09 viruses with 275Y substitution

13. May 2009-April 2010May 2010-April 2011 SourceTotal Tested Number H275Y Genotyped Number Phenotyped Number ResistantPercentageTotal Tested Number H275Y Genotyped Number Phenotyped Number ResistantPercentage Community109888221600.06826255771.0 Hospital44893855634451.02818273880491.7 Total55874737850450.835003363137561.6 US-CDC NIMR Detection of Antiviral resistant H1N1pdm09 viruses with 275Y substitution

14. A(H3N2) viruses Antigenic and genetic characterizations

16. Antigenic analysis of A (H3N2) viruses by HI tests Sept, 2010 –Feb, 2011 NIID CDC Mar –Aug, 2010 JPN, China, Taiwan, Korea, Mongol, Laos, Myanmar, Singapore JPN, China, Taiwan, Korea, Mongol, Laos, Myanmar, Singapore N+C America, EU, Asia, Africa, AU, NZ N+C America, EU, Asia, Africa, AU, NZ >8-fold low A/Perth/16-like 83% 17% =4-fold low 53% 42% 5%5% 5%5% >8-fold low =4-fold low 81% 72% 27% 1%1% 1%1% =4-fold low 19% NIMR EU, Africa C-CDC China A/Perth/16-like 91% >8-fold low 9%9% 9%9% Low HA viruses >8-fold low 5%5% 5%5% A/Perth/16-like 95% A/Perth/16-like 71% >8-fold low 29%

17. 2009/10 Late phase (2010, April to July ） 2010/11 Early phase (2010. Sept to 2011. Jan ） Majority clade JPN viruses Vaccine strain

18. Summary of A(H3N2) cartography(Cambridge University) A/Brisbane/10/07 A/Perth/16/09 2008/09 season 2009/10 season A/Brisbane/10/07 A/Victoria/208/09 A/Perth/16/09 A/Brisbane/10/07 A/Perth/16/09 CDC data NIID data A/Brisbane/10/07 A/Vic/208/09 cluster 2010/11 season A/Vic/208/09 cluster

19. B viruses Antigenic and genetic characterizations

21. 96% 4% 80% 20% 78% 22% 86% 14% 91% 9% China N+C America, EU, Asia, Africa, AU, NZ N+C America, EU, Asia, Africa, AU, NZ EU, Africa, ME Asia, HK AU, NZ, Pacific, SE Asia, E Asia NIID China CDC CDC NIMR Melbourne Proportion of B/Vic- and B/Yama-lineage viruses in the world B/Yama B/Vic Japan Mar -Aug 2010 B/Yama B/Vic 2% 98% B/Vic B/Yama B/Vic B/Yama B/Vic 65% 35% 84% 16% 83% 17% 100% Sept, 2010 –Feb, 2011

22. Antigenic analysis of B/Vic-lineage viruses by HI tests 4-low >8-low 1% Bris/60-like 99% 49% 40% 11% NIID CDC Mar -Aug 2010 Bris/60-like >8-low Sept, 2010 –Feb, 2011 Bris/60-like 4-low >8-low 86% 5%5% 5%5% 9%9% 9%9% 58% 40% 4-low >8-low 2%2% 2%2% Bris/60-like 98% >8-low 2%2% 2%2% 39% Bris/60-like 61% >8-low NIMR Bris/60-like 99% >8-low 1%1% 1%1% Bris/60-like 85% 15% >8-low China CDC

23. Vaccine strain 2009/10 Late phase (2010, April to July ） 2010/11 Early phase (2010. Sept to 2011. Jan ） B/Vic-lineage viruses

24. Antigenic cartography of the antigenic variant against B/Brisbane60/2008 with K165N substitution HI data from NIID 197N B/Brisbane/60 MDCKx/1 B/Brisbane/60 E4/E4 B/Brisbane/60 MDCKx/1 B/Brisbane/60 E4/E4 Receptor-binding site 197S N-linked glycan Lack of potential glycosylation site was observed in egg- grown virus Variants with 165N in B/Bris/60 clade

25. Antigenic cartography of B/Yamagata viruses (Cambridge University)

26. Vaccine viruses recommended by WHO 2011/12 (Northern Hem) season: an A/California/7/2009 (H1N1)-like virus an A/Perth/16/2009 (H3N2)-like virus a B/Brisbane/60/2008-like virus 2011/12 (Northern Hem) season: an A/California/7/2009 (H1N1)-like virus an A/Perth/16/2009 (H3N2)-like virus a B/Brisbane/60/2008-like virus No change from last season

27. Increase of Low HA A(H1N1)pdm09 viruses in Japan

28. Low HA A(H1N1)pdm09 viruses increased from Jan 2011

29. HA titration of recent A/H1N1pdm09 viruses using various RBCs StrainsSubtypeSample date Passage history HA titre TCID 50 /mLTCID 50 /HA 0.5%TRBC1%GRBC Reference A/Wisconsin/10/1998A/H1N11998C3/C3E2 +2 6432ND A/California/07/2009A/H1pdm2009/04/09E2 +3 32+/- ND A/NARITA/1/2009A/H1pdm2009/05/08E2 +1 324+/-ND A/NARITA/1/2009A/H1pdm2009/05/08MDCK 1 +2 16+/-32+/-ND A/Utah/20/2009A/H1pdm2009/07/25C 2 +1 6464+/-ND A/YAMAGATA/752/2009A/H1pdm2009/12/03MDCK 2 +1 648ND High HA A/FUKUSHIMA/112/2010A/H1pdm2010/08/10MDCK 2 +1 6464+/-7.7 7.8×10 5 A/CHIBA/17/2010A/H1pdm2010/08/10MDCK 1 +1 256128+/-7.7 2.0×10 5 Low HA A/NIIGATA/62/2011A/H1pdm2011/01/18MDCK 1 +2 22+/-5.7 2.5×10 5 A/GIFU-C/14/2011A/H1pdm2011/01/24MDCK 1 +2 42+/-6.5 7.9×10 5 A/HOKKAIDO/12/2011A/H1pdm2011/01/17MDCK 2 +2 426.3 5.0×10 5 A/SAPPORO/19/2011A/H1pdm2011/01/14MDCK 1 +2 425.5 7.9×10 4 A/SAKAI/6/2011A/H1pdm2011/01/07MDCK 1 +2 22+/-4.7 2.5×10 4 A/SHIGA/30/2011A/H1pdm2011/01/21MDCK 1 +2 42+/-6.3 5.0×10 5 A/KITAKYUSYU/1/2011A/H1pdm2011/01/04MDCK 1 +2 42+/-ND A/HIROSHIMA/24/2011A/H1pdm2011/01/14MDCK 3 +2 44+/-ND A/NIIGATA/53/2011A/H1pdm2011/01/17MDCK 1 +2 44+/-ND A/SAKAI/2/2011A/H1pdm2011/01/04MDCK 1 +2 42ND A/SHIGA/32/2011A/H1pdm2011/01/06MDCK 1 +2 42ND A/SHIGA/43/2011A/H1pdm2011/01/08MDCK 1 +2 42ND A/KAGAWA/1/2011A/H1pdm2011/01/31MDCK 0 +1 42+/-ND

30. December 2010 in Blue January 2011 in Green February 2011 in Orange March 2011 in Pink #: Fatal case @: Oseltamivir resistance Low: Low HA OITA/77/2011 FEB Low @ OITA/72/2011 FEB G155E/G @ HOKKAIDO/32/2011 JAN Low HIROSHIMA/45/2011-OR FEB @ KUMAMOTO-C/7/2011 JAN EHIME/4/2011 JAN Korea/664/2010.CDC DEC GIFU-C/31/2011 FEB Low FUKUOKA-C/37/2010 NOV HIROSHIMA/55/2011 FEB Low @ IWATE/1008/2011-OR JAN Low @ SAGAMIHARA/5/2011 JAN Low KAGAWA/1/2011 JAN Low @ SHIZUOKA/37/2011 FEB Low @ Gyeongnam/3110/2010 DEC G155G/E SHIMANE/140/2011 FEB Low NewHampshire/03/2011.CDC FEB SHIGA/43/2011 JAN Low FUKUOKA-C/39/2010 DEC California/23/2010.CDC OCT Connecticut/04/2011.CDC FEB Incheon/2434/2010 NOV WAKAYAMA-C/6/2011 JAN K153Q @ CHIBA/1027/2011 JAN Low @ TOTTORI/8/2011 JAN # K153E HIROSHIMA/50/2010 NOV ISHIKAWA/22183/2011 JAN Low SHIMANE/24/2011-OR JAN HIROSHIMA/49/2011 FEB Low @ AKITA/1/2011-OR JAN Low KITAKYUSYU/1/2011 JAN Low @ SHIZUOKA-C/8/2011 JAN Low KOBE/463/2011-OR JAN HIROSHIMA/22/2011 JAN Low KUMAMOTO/7/2011 JAN G155G/E KAGAWA/2/2011 FEB @ FUKUSHIMA/138/2010 DEC G155G/E AKITA/5/2011 FEB Low @ SHIGA/45/2011 JAN Low YOKOHAMA/29/2011-OR JAN @ NewYork/11/2010.CDC DEC YAMAGATA/752/09 DEC G155E Laos/O066/2010 NOV Washington/08/2011.CDC FEB Montana/06/2011.CDC MAR Nebraska/10/2011.CDC MAR Bangladesh/5513/2011.CDC FEB OKINAWA/40/2011 JAN @ Arkansas/01/2011.CDC JAN Georgia/3/2011.NIMR DEC HIROSHIMA/1/2011 JAN Florida/12/2011.CDC MAR Maryland/07/2011.CDC FEB @ Indiana/05/2011.CDC FEB Colorado/04/2011.CDC MAR HongKong/6931/2010.CDC DEC Wisconsin/11/2011.CDC FEB Michigan/02/2011.CDC FEB Georgia/51/2011.NIMR JAN England/404/2010.NIMR DEC Kentucky/09/2010.CDC NOV # G155E D222G Montana/03/2011.CDC FEB England/151/2010.NIMR NOV DARWIN/178/2010.Aus DEC DARWIN/2/2011.Aus JAN HIROSHIMA/66/2011 FEB @ Kansas/06/2011.CDC FEB Alaska/09/2011.CDC FEB Gyeonggi/2623/2010 NOV G155G/E SHIZUOKA/20/2011-OR JAN Low @ NIIGATA/1563/2010 DEC Texas/08/2011.CDC MAR Maryland/04/2011.CDC FEB @ Maine/03/2011.CDC MAR Georgia/25/2010.CDC DEC NARA/54/2011 FEB @ WAKAYAMA/49/2010 DEC WAKAYAMA-C/53/2010 DEC Christchurch/16/10E.Aus JUL D222N Soria/16/2011.NIMR JAN OSAKA-C/25/2010 DEC SAKAI/47/2010 DEC Taiwan/151/2010 AUG YAMAGATA/203/2011 FEB HIROSHIMA-C/28/2011 JAN YAMAGATA/54/2011 JAN Low Washington/09/2011.CDC MAR Pennsylvania/01/2011.CDC JAN VICTORIA/1204/2010.Aus OCT Mississippi/07/2011.CDC FEB Laos/I969/2010 OCT Shanghai-Zhangning/SWL1700/2010.CNIC DEC Myanmar/JP-S-026/10 JUL OSAKA/60/10 JUL England/195/09.CDC APR Utah/20/09.CDC JUL NARITA/1/09E MAY Mexico/InDRE4487/09 APR California/07/09E X179A.CDC California/07/09E.CDC APR 0.001 S143G A197T D97N S185T S83T A134T S183P N31D K146N S203T S162N N125D Vaccine Recent majority clade Low HA virus clade

31. Acknowledgement Influenza virus surveillance group in Japan Pathogen genomic center, NIID Drs. Motomura, Yokoyama and Sato Infectious Disease Surveillance Center, NIID Drs Yamashita, Yasui and Okabe National Influenza Centers WHO Collaborating Center for Reference and Research on Influenza US CDC, Atlanta (N. Cox, A. Klimov) NIMR, London (J. McCauley, R. Daniels) VIDRL, Melbourne (A. Kelso, I. Barr) China CDC, Beijing (Y. Shu, D. Wang) Cambridge University (D. Smith, C. Russel)