Wu Wai Lan, Chen Yixin, Wang Pui, Song Wenjun, Lau Siu-Ying, Rayner Jane M, Smith Gavin J D, Webster Robert G, Peiris J S Malik, Lin Tianwei, Xia Ningshao, Guan Yi, Chen Honglin
State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China.
J Virol. 2008 Feb;82(4):1798-807. doi: 10.1128/JVI.02256-07. Epub 2007 Dec 12.
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.
利用从5株H5N1病毒株产生的一组17种单克隆抗体,对代表主要基因分支和不同地理来源的2002年后H5N1病毒的抗原特性进行了研究。基于H5N1病毒7个分支在血凝抑制试验和基于细胞的中和试验中与单克隆抗体的交叉反应性,区分并鉴定了4个抗原组。鉴定出与H5N1毒株抗原性变异相关的基因多态性,并在对血凝素蛋白携带特定突变的重组H5N1病毒进行的抗原分析中进一步验证。在利用针对1和2分支H5N1病毒产生的单克隆抗体和雪貂抗血清进行的试验中,对其中一些基因变异的修饰显著提高了H5N1毒株的免疫原性和交叉反应性,表明这些位点代表具有抗原意义的氨基酸。这些结果为近年来流行的H5N1病毒株提供了全面的抗原特性,将有助于识别H5N1病毒新出现的抗原变异体,并有助于疫苗株的选择。