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

Seiya Yamayoshi; Mutsumi Ito; Ryuta Uraki; Tadahiro Sasaki; Kazuyoshi Ikuta; Yoshihiro Kawaoka

doi:10.1016/j.jinf.2017.12.004

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

J Infect. 2018 Feb;76(2):177-185. doi: 10.1016/j.jinf.2017.12.004. Epub 2017 Dec 14.

Authors

Seiya Yamayoshi¹, Mutsumi Ito¹, Ryuta Uraki¹, Tadahiro Sasaki², Kazuyoshi Ikuta², Yoshihiro Kawaoka³

Affiliations

¹ Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan.
² Department of Virology, Research Institute for Microbial Diseases, Osaka University, Japan.
³ Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA; Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Japan; ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Japan. Electronic address: yoshihiro.kawaoka@wisc.edu.

Abstract

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.

Keywords: Group 2; HA stem; Human monoclonal antibody; Influenza A virus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / immunology*
Antibodies, Monoclonal / isolation & purification
Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology*
Antibodies, Viral / isolation & purification
Epitopes / immunology*
Female
HEK293 Cells
Hemagglutinin Glycoproteins, Influenza Virus / immunology*
Humans
Immunoglobulin G / immunology
Immunoglobulin G / isolation & purification
Influenza A Virus, H3N2 Subtype / immunology*
Mice, Inbred BALB C
Mutation
Neutralization Tests

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Epitopes
Hemagglutinin Glycoproteins, Influenza Virus
Immunoglobulin G

Grants and funding

HHSN272201400008C/AI/NIAID NIH HHS/United States