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Journal of Virology, February 2008, p. 1798-1807, Vol. 82, No. 4
0022-538X/08/$08.00+0 doi:10.1128/JVI.02256-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Yixin Chen,3,4,
Pui Wang,1
Wenjun Song,1
Siu-Ying Lau,1
Jane M. Rayner,1
Gavin J. D. Smith,1
Robert G. Webster,5
J. S. Malik Peiris,1
Tianwei Lin,1,4
Ningshao Xia,3,4
Yi Guan,1,2* and
Honglin Chen1,2*
State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology and the Research Center of Infection and Immunology, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China,1 International Institute of Infection and Immunity, Shantou University, Shantou, People's Republic of China,2 National Institute of Diagnostics and Vaccine Development in Infectious Diseases,3 School of Life Sciences, Xiamen University, Xiamen, People's Republic of China,4 Virology Division, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 381055
Received 18 October 2007/ Accepted 26 November 2007
Antigenic profiles of post-2002 H5N1 viruses representing major genetic clades and various geographic sources were investigated using a panel of 17 monoclonal antibodies raised from five H5N1 strains. Four antigenic groups from seven clades of H5N1 virus were distinguished and characterized based on their cross-reactivity to the monoclonal antibodies in hemagglutination inhibition and cell-based neutralization assays. Genetic polymorphisms associated with the variation of antigenicity of H5N1 strains were identified and further verified in antigenic analysis with recombinant H5N1 viruses carrying specific mutations in the hemagglutinin protein. Modification of some of these genetic variations produced marked improvement to the immunogenicity and cross-reactivity of H5N1 strains in assays utilizing monoclonal antibodies and ferret antisera raised against clade 1 and 2 H5N1 viruses, suggesting that these sites represent antigenically significant amino acids. These results provide a comprehensive antigenic profile for H5N1 virus strains circulating in recent years and will facilitate the recognition of emerging antigenic variants of H5N1 virus and aid in the selection of vaccine strains.
Published ahead of print on 12 December 2007.
W.L.W. and Y.C. contributed equally to this study.
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