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Title: 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

Abstract

Highlights: • 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. - Abstract: 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 inmore » 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.« less

Authors:
;  [1];  [1]; ; ;  [2];  [1];  [3];  [4];  [5];  [6];  [3];
  1. Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand)
  2. National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand)
  3. Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan)
  4. Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa (Japan)
  5. Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka (Japan)
  6. Ina Laboratory, Medical and Biological Laboratories Corporation, Ltd., Ina, Nagano (Japan)
Publication Date:
OSTI Identifier:
22416764
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 452; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMINO ACIDS; HUMAN POPULATIONS; INFLUENZA; INFLUENZA VIRUSES; INHIBITION; LYMPHOCYTES; MONOCLONAL ANTIBODIES; MUTANTS; RECEPTORS; RESIDUES; VACCINES

Citation Formats

Boonsathorn, Naphatsawan, Panthong, Sumolrat, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Koksunan, Sarawut, Chittaganpitch, Malinee, Phuygun, Siripaporn, Waicharoen, Sunthareeya, Prachasupap, Apichai, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Sasaki, Tadahiro, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Kubota-Koketsu, Ritsuko, Yasugi, Mayo, Ono, Ken-ichiro, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Arai, Yasuha, and others, and. 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. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2014.09.008.
Boonsathorn, Naphatsawan, Panthong, Sumolrat, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Koksunan, Sarawut, Chittaganpitch, Malinee, Phuygun, Siripaporn, Waicharoen, Sunthareeya, Prachasupap, Apichai, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Sasaki, Tadahiro, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Kubota-Koketsu, Ritsuko, Yasugi, Mayo, Ono, Ken-ichiro, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Arai, Yasuha, & others, and. 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. United States. https://doi.org/10.1016/J.BBRC.2014.09.008
Boonsathorn, Naphatsawan, Panthong, Sumolrat, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Koksunan, Sarawut, Chittaganpitch, Malinee, Phuygun, Siripaporn, Waicharoen, Sunthareeya, Prachasupap, Apichai, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Sasaki, Tadahiro, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Kubota-Koketsu, Ritsuko, Yasugi, Mayo, Ono, Ken-ichiro, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Arai, Yasuha, and others, and. 2014. "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". United States. https://doi.org/10.1016/J.BBRC.2014.09.008.
@article{osti_22416764,
title = {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},
author = {Boonsathorn, Naphatsawan and Panthong, Sumolrat and Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development and Koksunan, Sarawut and Chittaganpitch, Malinee and Phuygun, Siripaporn and Waicharoen, Sunthareeya and Prachasupap, Apichai and Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development and Sasaki, Tadahiro and Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development and Kubota-Koketsu, Ritsuko and Yasugi, Mayo and Ono, Ken-ichiro and Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development and Arai, Yasuha and others, and},
abstractNote = {Highlights: • 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. - Abstract: 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.},
doi = {10.1016/J.BBRC.2014.09.008},
url = {https://www.osti.gov/biblio/22416764}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 452,
place = {United States},
year = {Fri Sep 26 00:00:00 EDT 2014},
month = {Fri Sep 26 00:00:00 EDT 2014}
}