| 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. |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/56866 |
| Appears in Collections: | 人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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