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

Itoh, Yasushi

Yoshida, Reiko

Shichinohe, Shintaro

Higuchi, Megumi

Ishigaki, Hirohito

Nakayama, Misako

Pham, Van Loi

Ishida, Hideaki

Kitano, Mitsutaka

Arikata, Masahiko

Kitagawa, Naoko

Mitsuishi, Yachiyo

Ogasawara, Kazumasa

Tsuchiya, Hideaki

Hiono, Takahiro

Okamatsu, Masatoshi

Sakoda, Yoshihiro

Kida, Hiroshi

Ito, Mutsumi

Mai, Le Quynh

Kawaoka, Yoshihiro

Miyamoto, Hiroko

Ishijima, Mari

Igarashi, Manabu

Suzuki, Yasuhiko

Takada, Ayato

  • NDC 649
  • 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.
PublisherPublic Library of Science
Date Issued 2014-06-12
NIItypejournal article
Identifier URI
  • isIdenticalTo DOI
    • ISSN 1553-7366
    • PLOS Pathogens
    10(6), e1004192