A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

作者：Boonsathorn Naphatsawan; Panthong Sumolrat; Koksunan Sarawut; Chittaganpitch Malinee; Phuygun Siripa****; Waicharoen Sunthareeya; Prachasupap Apichai; Sasaki Tadahiro; Kubota Koketsu Ritsuko; Yasugi Mayo; Ono Ken ichiro; Arai Yasuha; Kurosu Takeshi; Sawanpanyalert Pathom; Ikuta Kazuyoshi^*; Watanabe Yohei

来源：Biochemical and Biophysical Research Communications, 2014, 452(3): 865-870.

DOI：10.1016/j.bbrc.2014.09.008

• Influenza A virus
• Human monoclonal antibody
• Heterosubtypic neutralizing antibody
• Conserved epitope in HA head region

Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb hetero-subtypically neutralizes group 1 influenza A viruses, including seasonal Hi NI, 2009 pandemic HI NI (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.

• 出版日期2014-9-26