[HTML][HTML] Cross-protective potential of a novel monoclonal antibody directed against antigenic site B of the hemagglutinin of influenza A viruses
R Yoshida, M Igarashi, H Ozaki, N Kishida… - PLoS …, 2009 - journals.plos.org
R Yoshida, M Igarashi, H Ozaki, N Kishida, D Tomabechi, H Kida, K Ito, A Takada
PLoS pathogens, 2009•journals.plos.orgThe 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 …
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 …
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.
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