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

• Published in: Biochemical and biophysical research communications Vol. 452; no. 3; pp. 865 - 870
• Main Authors: Boonsathorn, Naphatsawan, Panthong, Sumolrat, Koksunan, Sarawut, Chittaganpitch, Malinee, Phuygun, Siripaporn, Waicharoen, Sunthareeya, Prachasupap, Apichai, Sasaki, Tadahiro, Kubota-Koketsu, Ritsuko, Yasugi, Mayo, Ono, Ken-ichiro, Arai, Yasuha, Kurosu, Takeshi, Sawanpanyalert, Pathom, Ikuta, Kazuyoshi, Watanabe, Yohei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26-09-2014
• Subjects: 60 APPLIED LIFE SCIENCES; Amino Acid Sequence; AMINO ACIDS; Animals; Antibodies, Monoclonal - biosynthesis; Antibodies, Neutralizing - biosynthesis; Antibodies, Viral - biosynthesis; Antigens, Viral - chemistry; Antigens, Viral - immunology; Conserved epitope in HA head region; Cross Protection; Epitope Mapping; Epitopes - chemistry; Epitopes - immunology; Hemagglutination Inhibition Tests; Hemagglutinin Glycoproteins, Influenza Virus - chemistry; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Heterosubtypic neutralizing antibody; Human monoclonal antibody; HUMAN POPULATIONS; Humans; Hybridomas - immunology; INFLUENZA; Influenza A virus; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H9N2 Subtype - immunology; Influenza Vaccines - administration & dosage; INFLUENZA VIRUSES; Influenza, Human - immunology; Influenza, Human - prevention & control; Influenza, Human - virology; INHIBITION; LYMPHOCYTES; Male; Mice; Models, Molecular; Molecular Sequence Data; MONOCLONAL ANTIBODIES; MUTANTS; Protein Conformation; RECEPTORS; RESIDUES; Vaccination; VACCINES; Young Adult; Influenza A virus; Heterosubtypic neutralizing antibody; Conserved epitope in HA head region; Human monoclonal antibody
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.09.008

•A human monoclonal antibody against influenza virus was produced from a volunteer.•The antibody was generated from the PBMCs of the volunteer using the fusion method.•The antibody neutralized heterosubtypically group 1 influenza A viruses (H1 and H9).•The antibody targeted a novel epitope in globular head region of the hemagglutinin.•Sequences of the identified epitope are highly conserved among H1 and H9 subtypes.
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 heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (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.