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PLoS Pathog. 2014 Jun 12;10(6):e1004192. doi: 10.1371/journal.ppat.1004192. eCollection 2014 Jun.

Protective efficacy of passive immunization with monoclonal antibodies in animal models of H5N1 highly pathogenic avian influenza virus infection.

Author information

1
Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan.
2
Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan.
3
Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
4
Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan; Infectious Diseases, Medicinal Research Laboratories, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.
5
Research Center for Animal Life Science, Shiga University of Medical Science, Otsu, Shiga, Japan.
6
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
7
National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.
8
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, United States of America.
9
Division of Bioinformatics, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan.

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.

PMID:
24945244
PMCID:
PMC4055766
DOI:
10.1371/journal.ppat.1004192
[Indexed for MEDLINE]
Free PMC Article

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