Human protective monoclonal antibodies against the HA stem of group 2 HAs derived from an H3N2 virus-infected human.

OBJECTIVES: Broadly reactive human monoclonal antibodies against the HA stem of influenza A virus are being developed as therapeutic agents as well as to understand the epitopes that are essential for a universal influenza virus vaccine.

METHODS: We isolated and characterized two hetero-reactive human monoclonal antibodies from an H3N2 virus-infected human.

RESULTS: These antibodies, which are predominantly bound to the HA stem of group 2 HAs, used IGHV3-66 and IGHV4-38-2 germline genes, respectively. They possessed in vitro neutralizing ability, and in vivo protective efficacy against lethal infection with H3N2 or H7N9 virus. Escape mutations revealed that one of the protective antibodies recognized the α-helix A of HA2, and the other recognized the C-terminal portion of the fusion peptide and the β-sheet that precedes the α-helix A of HA2.

CONCLUSIONS: Of many human protective monoclonal antibodies against the HA stem, two human protective monoclonal antibodies were isolated in this study that predominantly recognize epitopes on the HA stem of group 2 and use unique IGHV3-66 and IGHV4-38-2 germline genes.