| Institution: | 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 & Biological Laboratories Corporation, Ltd., Ina, Nagano, Japan;g Food and Drug Administration, Ministry of Public Health, Muang, Nonthaburi, Thailand;h Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo, Japan |
| 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. |
