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Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection

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Title: Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection
Authors: Itoh, Yasushi Browse this author →KAKEN DB
Yoshida, Reiko Browse this author →KAKEN DB
Shichinohe, Shintaro Browse this author
Higuchi, Megumi Browse this author
Ishigaki, Hirohito Browse this author
Nakayama, Misako Browse this author
Pham, Van Loi Browse this author
Ishida, Hideaki Browse this author
Kitano, Mitsutaka Browse this author
Arikata, Masahiko Browse this author
Kitagawa, Naoko Browse this author
Mitsuishi, Yachiyo Browse this author
Ogasawara, Kazumasa Browse this author →KAKEN DB
Tsuchiya, Hideaki Browse this author →KAKEN DB
Hiono, Takahiro Browse this author →KAKEN DB
Okamatsu, Masatoshi Browse this author →KAKEN DB
Sakoda, Yoshihiro Browse this author →KAKEN DB
Kida, Hiroshi Browse this author →KAKEN DB
Ito, Mutsumi Browse this author
Mai, Le Quynh Browse this author
Kawaoka, Yoshihiro Browse this author →KAKEN DB
Miyamoto, Hiroko Browse this author
Ishijima, Mari Browse this author
Igarashi, Manabu Browse this author →KAKEN DB
Suzuki, Yasuhiko Browse this author →KAKEN DB
Takada, Ayato Browse this author →KAKEN DB
Issue Date: 12-Jun-2014
Publisher: Public Library of Science
Journal Title: PLOS Pathogens
Volume: 10
Issue: 6
Start Page: e1004192
Publisher DOI: 10.1371/journal.ppat.1004192
Abstract: 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.
Type: article
Appears in Collections:人獣共通感染症リサーチセンター (Research Center for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 高田 礼人

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