OFFLU contribution to the WHO vaccine selection meeting

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1 OFFLU contribution to the WHO vaccine selection meeting WHO Consultation on the Composition of Influenza Vaccines for the Southern Hemisphere 0 (0- Feb 0, Geneva) Giovanni Cattoli OFFLU Annual technical meeting 4-5 April 0 Royal Holloway, London

2 Acknowledgements Filip Claes, Mia Kim Richard Webby, Gwenaelle Dauphin, Ian Brown, Paul Selleck OFFLU Secretariat WHO With gratitude to all the contributing labs and scientists

3 OFFLU sources of information Genetic information OIE/FAO reference centers National laboratories FAO national and regional offices Epidemiological info EMPRES-i WAHID

4 Distribution of H5 outbreaks: Sept 0 to 3 Feb 0 (source: EMPRES-i - includes WAHID entries) Country chicken / plus duck/ geese unspecified bird wild Grand Total Bangladesh 0 0 Bhutan Cambodia China 3 3 China, Hong Kong SAR Egypt Hong Kong 4 6 India 4 7 Indonesia Iran (Islamic Republic of) 3 Nepal Viet Nam 4 6 Grand Total

5 Evolution of OFFLU contribution to VCM Sep-0 feb- Sep- feb- # labs providing genetic data # labs providing antigenic data

6 OFFLU H5 sequences: Sept 0 to 3 Feb 0 39 Sequences from 3 active H5N clades 0: RED ITALICS (non-public), RED BOLD (public) : PURPLE ITALICS (non-public) Clade.. Country Egypt Israel chicken ducks duck goose.. Total... Egypt... Total.3.. Bangladesh 4 Iran Nepal Tibet *.3.. Total 7 3 Grand Total 30 5 * not reported in epidemiologic data Grand Total turkey

7 WHO, February 0

8 CLADE../... Preliminary residue analysis All the novel Egyptian.. viruses included have 9 deletion and substitution I5T (RBS) AA changes in HA..: 9- (compared to 3/07)...: 8- (compared to NAMRU/008 )

9 CLADE.3.. Iran, Bangladesh, PR China, Nepal Hubei-like viruses Residue analysis No AA substitutions in potential RBS 5-9 AA changes in HA compared to A/Hubei//0

10 Ferret antisera used to generate antigenic (HI) data sera clade clade antigen Anti-rg-A/VN/03/04 rg-a/vn/03/04 Anti-rg-A/Duck/Hunan/795/00. rg-a/cambodia/r0h05050/007 (no homolog) Anti-rg-A/Bar-Headed goose/qinghai/ia/05.. rg-a/duck/hunan/795/00 Anti-rg-A/Whooper Swan/Mongolia/44/05.. rg-a/bar-headed goose/qinghai/ia/05 Anti-A/turkey/Israel/364/006 (no homolog).. rg-a/whooper Swan/Mongolia/44/05 Anti-A/turkey/Islamabad-Pakistan/NARC-787/007 (no homolog).. rg-a/india/niv-33487/06 (no homolog) Anti-rg-A/Egypt/3/ rg-a/egypt/3-namru3/07 Anti-rg/A/Common Magpie/Hong Kong/505/ rg-a/egypt/3300-namru3/08 (no homolog) Anti-A/common buzzard/bulgaria/38wb/00 (no homolog) rg-a/common Magpie/Hong Kong/505/007 Anti-A/Muscovy duck/vietnam/33/007 (no homolog) rg-a/japanese White Eye/HongKong/038/06 Anti-A/barn swallow/hk/6/00 (no homolog) rg-a/ck/hk/ap56/08 Anti-rg-A/Japanese White Eye/HongKong/038/ rg-a/duck/laos/395/06 Anti-rg-A/Ck/Hk/AP56/ rg-a/anhui/0/005 (no homolog) Anti-rg-A/Duck/Laos/395/ rg-a/goose/guiyan/337/06 Anti-rg-A/Goose/Guiyan/337/ rg-a/chicken/vietnam/ncvd-06/08 (no homolog)

11 WHO ferret anti-sera panel Test antigens Antigenic data for WHO ferret panel VCM FEBRUARY 0 HI/chicken/sera treatment: :4 RDE; O/N 37 C; 56 CX30min; +PBS: final diluition :0 clade.. Anti-rg- A/Egypt/3/0 7 A/Common Magpie/Hong Kong/505/ 007 clade.3. A/common buzzard/bulg aria/38wb/ 00 (no A/Muscovy duck/vietna m/33/007 (no homolog) Anti-A/barn swallow/hk/ 6/00 (no homolog) Lab clade Test antigens St Judes.. rg-a/egypt/3-namru3/ <0 IZSVe.. sub A A/chicken/Egypt/VIR /VRLCU/0 80 <0 0 0 <0 IZSVe.. sub A A/chicken/Egypt/VIR /VRLCU/ <0 0 <0 IZSVe.. sub A A/chicken/Egypt/VIR /VRLCU/0 80 <0 0 0 <0 IZSVe.. sub A A/chicken/Egypt/VIR /VRLCU/0 80 <0 0 0 <0 IZSVe.. sub A A/chicken/Egypt/VIR4453-7/VRLCU/00 0 <0 0 0 <0 IZSVe.. sub A A/chicken/Egypt/VIR /VRLCU/0 0 <0 <0 <0 <0 IZSVe.. sub A A/chicken/Egypt/VIR /00 40 <0 0 <0 <0 IZSVe.. sub B A/chicken/Egypt/VIR4453-9/VRLCU/00 40 <0 <0 <0 <0 IZSVe.. sub B A/chicken/Egypt/VIR4453-8/VRLCU/00 <0 80 <0 <0 <0 IZSVe.3. A/goose/Bangladesh/Vir534-/ <0 <0 St Judes.3. rg-a/common Magpie/Hong Kong/505/ <0 <0 AHVLA.. A/turkey/Israel/34/ 80 <0 n/d n/d <0 AHVLA.3. A/crow/Nepal/84/ <0 40 n/d n/d <0 AHVLA.3. A/chicken/Nepal/447/ 0 40 n/d n/d <0

12 Antigenic data for WHO ferret panel VCM FEBRUARY 0 HI/chicken/sera treatment: :4 RDE; O/N 37 C; 56 CX30min; +PBS: final diluition :0 CLADE../.. clade.. A/Common Anti-rg- Magpie/Hong A/Egypt/3/0 Kong/505/ clade.3. A/common buzzard/bulg aria/38wb/ 00 (no A/Muscovy duck/vietna m/33/007 (no homolog) Anti-A/barn swallow/hk/ 6/00 (no homolog) Lab clade Test antigens St Judes.. rg-a/egypt/3-namru3/ <0 IZSVe.. sub A A/chicken/Egypt/VIR /VRLCU/0 80 <0 0 0 <0 IZSVe.. sub A A/chicken/Egypt/VIR /VRLCU/ <0 0 <0 IZSVe.. sub A A/chicken/Egypt/VIR /VRLCU/0 80 <0 0 0 <0 IZSVe.. sub A A/chicken/Egypt/VIR /VRLCU/0 80 <0 0 0 <0 IZSVe.. sub A A/chicken/Egypt/VIR4453-7/VRLCU/00 0 <0 0 0 <0 IZSVe.. sub A A/chicken/Egypt/VIR /VRLCU/0 0 <0 <0 <0 <0 IZSVe.. sub A A/chicken/Egypt/VIR /00 40 <0 0 <0 <0 IZSVe.. sub B A/chicken/Egypt/VIR4453-9/VRLCU/00 40 <0 <0 <0 <0 IZSVe.. sub B A/chicken/Egypt/VIR4453-8/VRLCU/00 <0 80 <0 <0 <0 IZSVe.3. A/goose/Bangladesh/Vir534-/ <0 <0 St Judes.3. rg-a/common Magpie/Hong Kong/505/ <0 <0 AHVLA.. A/turkey/Israel/34/ 80 <0 n/d n/d <0 AHVLA.3. A/crow/Nepal/84/ <0 40 n/d n/d <0 AHVLA.3. A/chicken/Nepal/447/ 0 40 n/d n/d <0 AA substitutions compared to the other novel viruses N/D55A Antigenic site A D/S0N Antigenic site A R89K Antigenic site B S0N Antigenic site A T5I Antigenic site B K5E Antigenic site B I90L Antigenic site B

13 OFFLU Laboratory ring trial 3 OFFLU laboratories involved (IZSVe-Italy; AHVLA- UK; AAHL-AUS). Main purpose - evaluate the level of standardization and harmonization among the OFFLU laboratories of the HI methodology applied on ferret sera and avian influenza antigens according to the WHO standards. Mat&Meth - A panel of 5 ferret sera and H5N antigens belonging to different clades was provided by WHO CC -St Jude to all the 3 laboratories together with the protocol to be applied.

14 Ferret antisera used to generate HI data and included in the ring trial sera clade clade antigen Anti-rg-A/VN/03/04 rg-a/vn/03/04 Anti-rg-A/Duck/Hunan/795/00. rg-a/cambodia/r0h05050/007 (no homolog) Anti-rg-A/Bar-Headed goose/qinghai/ia/05.. rg-a/duck/hunan/795/00 Anti-rg-A/Whooper Swan/Mongolia/44/05.. rg-a/bar-headed goose/qinghai/ia/05 Anti-A/turkey/Israel/364/006 (no homolog).. rg-a/whooper Swan/Mongolia/44/05 Anti-A/turkey/Islamabad-Pakistan/NARC-787/007 (no homolog).. rg-a/india/niv-33487/06 (no homolog) Anti-rg-A/Egypt/3/ rg-a/egypt/3-namru3/07 Anti-rg/A/Common Magpie/Hong Kong/505/ rg-a/egypt/3300-namru3/08 (no homolog) Anti-A/common buzzard/bulgaria/38wb/00 (no homolog) rg-a/common Magpie/Hong Kong/505/007 Anti-A/Muscovy duck/vietnam/33/007 (no homolog) rg-a/japanese White Eye/HongKong/038/06 Anti-A/barn swallow/hk/6/00 (no homolog) rg-a/ck/hk/ap56/08 Anti-rg-A/Japanese White Eye/HongKong/038/ rg-a/duck/laos/395/06 Anti-rg-A/Ck/Hk/AP56/ rg-a/anhui/0/005 (no homolog) Anti-rg-A/Duck/Laos/395/ rg-a/goose/guiyan/337/06 Anti-rg-A/Goose/Guiyan/337/ rg-a/chicken/vietnam/ncvd-06/08 (no homolog)

15 Ring trial outcomes overall the results are consistent between the 3 laboratories with variations in the HI titres limited to ± log dilution in the vast majority of cases. Basic statistical analysis performed on the results of the 3 labs (Kendall s coefficient of Concordance)

16 OFFLU H9N sequences: Sept 0 to 3 Feb 0 Year Country chicken duck quail turkey Grand Total 003 Iran 003 Total 009 Viet Nam Total Egypt Netherlands 00 Total 0 China Egypt 3 4 Nepal Netherlands Saudi Arabia UAE 0 Total 7 9 Grand Total

17 H9N (HA) Egypt Vietnam & China Vietnam & Europe

18 Future activities Standardized panel of reference antigens and ferret sera to be distributed among OFFLU Labs WHO CC-OFFLU labs harmonized phylogenetic tree backbone / residue analysis Antigenic data on H9N Candidate vaccine strains from one OFFLU lab shipped to WHO-CC (CDC) PIP framework

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