Antigenic cartography of H5 viruses

Transcription

1 14th joint annual meeting of the national reference laboratories for AI and ND Brussels, April 10, 2008 Antigenic cartography of H5 viruses Ron A.M. Fouchier, PhD. Professor Molecular Virology National Influenza Center and Department of Virology, Erasmus MC

2 A/H5N1 virus - Genetic variation - Source:

3 A/H5N1 virus Antigenic properties; hemagglutination inhibition (HI) Source:

4 Antigenic cartography - H3N2, 1968-present - Antigenic cartography: Employs a suite of software packages to analyze binding assay data with MDS algorithms. Enables quantitative analysis and visualization of antigenic properties of influenza virus (HI data) Multi Dimensional Scaling (MDS) algorithms Error function: E= ij e(d ij,d ij ) Smith et al., Science 305, (2004)

5 Antigenic cartography - Applications - Smith et al., Science 305, (2004); Method description + application to flu (A/H3N2) Smith et al., Discovery Medicine, 4, (2004). Method explanation in lay terms Real-time application for H3N2 vaccine strain selection within the WHO global influenza surveillance network Can these methods be applied to H5 HI datasets?

6 H5 influenza - Antigenic map, up to 2005/ Data from EMC & WER RBC: horse, turkey, chicken Sera: Ferret post infection Ferret post vaccination Rabbit post vaccination Bird post infection Bird post vaccination NOT compatible with: Chicken hyperimmune sera Vaccine strains: A/Vietnam/1194/2004-like virus A/Indonesia/5/2005-like virus A/Bar headed goose/qinghai/1a/2005-like virus A/Anhui/1/2005-like virus

7 H5 antigenic cartography - Using hyperimmunized chicken sera to make maps - Data provided by VLA, Jill Banks & Ian Brown -Very robust maps; excellent HI data -Double immunized chicken sera

8 H5 influenza map - Conclusions - - H5 HI data from different labs (e.g. EMC, CDC, St Jude, HKU) are in agreement (but NOT with labs using hyperimmunized chicken antisera for HI) - Clades that include viruses affecting humans (0, 1, 2.1, 2.2, 2.3) are antigenically distinct. - Antigenic differences, as measured with ferret sera, are sufficiently large (>> 4-fold HI) to warrant selection of vaccine candidates for each clade (Note: extrapolation from H1/H3) - Information on strains outside of clades 0, 1, 2.1, 2.2, 2.3 is scarce - Until 05/ 06 there was little antigenic drift WITHIN clades; later years under investigation

9 H5 influenza map - Other considerations - When we trust the antigen positions / antigenic relationships: - Can we say something reasonable about the serum positions / serum (cross-) reactivity? (e.g. for vaccine evaluation)

10 H5 influenza - Antigenic map, up to 2005/ Antisera to classical H5 strains Antisera to HPAI H5N1 strains

11 H5 antigenic maps - Rate of antigenic change (until 2005) - Calculate, based on rate of antigenic evolution (or emergence of new clades) and breadth of immune response induced by a particular vaccine: HOW LONG CAN WE USE THIS VACCINE?

12 Veterinary H5 vaccine - Analysis of serum antibodies - Dutch zoos Birds (>3000) vaccinated with water in oil adjuvanted WIV A/Duck/Pottsdam/1402/86 (H5N2) Two s.c. shots, 6 weeks apart, dose depending on bodyweight After one shot: GMT 37 (95% CI 25-53), 50% >HI 40 After two shots: GMT 190 (95% CI ), 80% >HI 40 Post-vaccination sera (28 birds, 7 orders) measured in HI against prototypes for clades: - Classical (A/Mallard/Netherlands/3/1999) - 0 (A/Hongkong/156/1997) - 1 (A/Vietnam/1194/2004) (A/Indonesia/1/2005) (A/Turkey/Turkey/1/2005) Philippa et al., Vaccine 25: (2007).

13 Veterinary H5 vaccine - Analysis of serum antibodies -

14 H5 antigenic maps - Vaccine evaluation - Now: homologous titer Bad Should evaluate: - Titer of immune response - Focus of immune response - Breadth of immune response Good Bad Good

15 Conclusions - Antigenic cartography & antibody landscapes - - Antigenic cartography offers visualization and quantitative analysis of antigenic differences between circulating strains; introduces agreement between labs - At least 6 antigenic clades of H5 exist, probably more, some MAY be drifting? - Cartography enables visualization and quantitative analysis of antibody responses (titer, focus, breadth), in relation to antigenic variation of H5 strains - Antigenic cartography and antibody landscapes facilitate quantitative and qualitative comparison of data from different vaccine trials - Antigenic cartography and antibody landscapes facilitate analysis of the effects of pre-vaccination antibodies, and prime/boost strategies with different strains (original antigenic sin, etc.) - Antigenic cartography may aid in H5N1 serosurveillance studies in wild birds

16 Acknowledgements Department of Zoology, Cambridge University (UK) Terry Jones, Collin Russell, Eugene Skepner, Ana Mosterin, David Burke, Dan Horton, Nicola Lewis, Margaret MacKinnon, Derek Smith National Influenza Center, Department of Virology, Erasmus Medical Center Emmie de Wit, Vincent Munster, Juthatip Keawcharoen, Bjorn Koel, Theo Bestebroer, Monique Spronken, Chantal Baas, Pascal Lexmond, Ruud van Beek, Rob van Lavieren, Guido van de Net, Walter Beyer, Jan de Jong, Guus Rimmelzwaan, Ab Osterhaus Centers for Disease Control and Prevention (USA) Alexander Klimov, Ruben Donis, Nancy Cox St Jude Children s Research Hospital (USA) Robert Webster, Scott Krauss, Richard Webby IZSVe (Italy) Ilaria Capua, Maria Serena Beato Southeast Poultry Research Labs (USA) David Swayne, Erica Spackman Community Reference Laboratory, VLA (UK) Ian Brown, Jill Banks, Budhipa Choudhury Japfa Comfeed (Indonesia) Teguh Prajitno NIVAREC WHO, FAO, OIE, OFFLU