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Title	en Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection
Creator	en Itoh, Yasushi NRID 1000090324566 en Yoshida, Reiko NRID 1000080435966 en Shichinohe, Shintaro en Higuchi, Megumi en Ishigaki, Hirohito en Nakayama, Misako en Pham, Van Loi en Ishida, Hideaki en Kitano, Mitsutaka en Arikata, Masahiko en Kitagawa, Naoko en Mitsuishi, Yachiyo en Ogasawara, Kazumasa NRID 1000020169163 en Tsuchiya, Hideaki NRID 1000010378440 en Hiono, Takahiro NRID 1000000775819 en Okamatsu, Masatoshi NRID 1000000507163 en Sakoda, Yoshihiro NRID 1000040333637 en Kida, Hiroshi NRID 1000010109506 en Ito, Mutsumi en Mai, Le Quynh en Kawaoka, Yoshihiro NRID 1000070135838 en Miyamoto, Hiroko en Ishijima, Mari en Igarashi, Manabu NRID 1000010374240 en Suzuki, Yasuhiko NRID 1000090206540 en Takada, Ayato NRID 1000010292062
Accessrights	open access
Rights	http://creativecommons.org/licenses/by/4.0/ en Creative Commons Attribution 4.0 International
Subject	NDC 649
Description	Abstract en Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype often cause severe pneumonia and multiple organ failure in humans, with reported case fatality rates of more than 60%. To develop a clinical antibody therapy, we generated a human-mouse chimeric monoclonal antibody (MAb) ch61 that showed strong neutralizing activity against H5N1 HPAI viruses isolated from humans and evaluated its protective potential in mouse and nonhuman primate models of H5N1 HPAI virus infections. Passive immunization with MAb ch61 one day before or after challenge with a lethal dose of the virus completely protected mice, and partial protection was achieved when mice were treated 3 days after the challenge. In a cynomolgus macaque model, reduced viral loads and partial protection against lethal infection were observed in macaques treated with MAb ch61 intravenously one and three days after challenge. Protective effects were also noted in macaques under immunosuppression. Though mutant viruses escaping from neutralization by MAb ch61 were recovered from macaques treated with this MAb alone, combined treatment with MAb ch61 and peramivir reduced the emergence of escape mutants. Our results indicate that antibody therapy might be beneficial in reducing viral loads and delaying disease progression during H5N1 HPAI virus infection in clinical cases and combined treatment with other antiviral compounds should improve the protective effects of antibody therapy against H5N1 HPAI virus infection.
Publisher	en Public Library of Science
Date	Issued2014-06-12
Language	eng
Resource Type	journal article
Version Type	VoR
Identifier	HDL http://hdl.handle.net/2115/56866
Relation	isIdenticalTo DOI https://doi.org/10.1371/journal.ppat.1004192
Journal	PISSN 1553-7366 en PLOS Pathogens Volume Number10 Issue Number6 Page Starte1004192
File	fulltext ppat.1004192.pdf 3.35 MB (application/pdf) Issued2014-06-12
Oaidate	2023-07-26