Cross-Protective Potential of a Novel Monoclonal Antibody Directed against Antigenic Site B of the Hemagglutinin of Influenza A Viruses

PLoS Pathogens

Hiroshi Kida¹  Manabu Igarashi¹  Reiko Yoshida¹  Daisuke Tomabechi¹  Ayato Takada¹  Hiroichi Ozaki²  Noriko Kishida³  Kimihito Ito⁴ 

[1] Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo, Hokkaido, Japan;Department of Veterinary Microbiology, Faculty of Agriculture, Tottori University, Tottori, Japan;Laboratory of Influenza Viruses, Department of Virology III, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan;Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan

关键词: Influenza A virus;    Antibodies;    Enzyme-linked immunoassays;    Wireless sensor networks;    Influenza viruses;    Amino acid substitution;    Influenza;    DNA sequence analysis;   

DOI  :  10.1371/journal.ppat.1000350

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The hemagglutinin (HA) of influenza A viruses has been classified into sixteen distinct subtypes (H1–H16) to date. The HA subtypes of influenza A viruses are principally defined as serotypes determined by neutralization or hemagglutination inhibition tests using polyclonal antisera to the respective HA subtypes, which have little cross-reactivity to the other HA subtypes. Thus, it is generally believed that the neutralizing antibodies are not broadly cross-reactive among HA subtypes. In this study, we generated a novel monoclonal antibody (MAb) specific to HA, designated MAb S139/1, which showed heterosubtypic cross-reactive neutralization and hemagglutination inhibition of influenza A viruses. This MAb was found to have broad reactivity to many other viruses (H1, H2, H3, H5, H9, and H13 subtypes) in enzyme-linked immunosorbent assays. We further found that MAb S139/1 showed neutralization and hemagglutination-inhibition activities against particular strains of H1, H2, H3, and H13 subtypes of influenza A viruses. Mutant viruses that escaped neutralization by MAb S139/1 were selected from the A/Aichi/2/68 (H3N2), A/Adachi/2/57 (H2N2), and A/WSN/33 (H1N1) strains, and sequence analysis of the HA genes of these escape mutants revealed amino acid substitutions at positions 156, 158, and 193 (H3 numbering). A molecular modeling study showed that these amino acids were located on the globular head of the HA and formed a novel conformational epitope adjacent to the receptor-binding domain of HA. Furthermore, passive immunization of mice with MAb S139/1 provided heterosubtypic protection. These results demonstrate that MAb S139/1 binds to a common antigenic site shared among a variety of HA subtypes and neutralizes viral infectivity in vitro and in vivo by affecting viral attachment to cells. The present study supports the notion that cross-reactive antibodies play some roles in heterosubtypic immunity against influenza A virus infection, and underscores the potential therapeutic utility of cross-reactive antibodies against influenza.

【 授权许可】

CC BY