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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection
PLoS Pathogens, Volume 10, No. 6, Article e1004192, Year 2014
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Description
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. © 2014 Itoh et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC4055766/bin/ppat.1004192.s001.tiff
https://efashare.b-cdn.net/share/pmc/articles/PMC4055766/bin/ppat.1004192.s002.tiff
https://efashare.b-cdn.net/share/pmc/articles/PMC4055766/bin/ppat.1004192.s003.tiff
https://efashare.b-cdn.net/share/pmc/articles/PMC4055766/bin/ppat.1004192.s004.tiff
https://efashare.b-cdn.net/share/pmc/articles/PMC4055766/bin/ppat.1004192.s005.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC4055766/bin/ppat.1004192.s006.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC4055766/bin/ppat.1004192.s007.docx
Authors & Co-Authors
Yoshida, Reiko
Japan, Sapporo
Hokkaido University
Hiono, Takahiro
Japan, Sapporo
Hokkaido University
Okamatsu, Masatoshi
Japan, Sapporo
Hokkaido University
Sakoda, Yoshihiro
Japan, Sapporo
Hokkaido University
Kida, Hiroshi
Japan, Sapporo
Hokkaido University
Ito, Mutsumi
Japan, Tokyo
The University of Tokyo
Lê, Maithi Quynh
Viet Nam, Hanoi
National Institute of Hygiene and Epidemiology Hanoi
Kawaoka, Yoshihiro K.
Japan, Tokyo
The University of Tokyo
United States, Madison
University of Wisconsin-madison
Miyamoto, Hiroko
Japan, Sapporo
Hokkaido University
Ishijima, Mari
Japan, Sapporo
Hokkaido University
Igarashi, Manabu
Japan, Sapporo
Hokkaido University
Suzuki, Yasuhiko
Japan, Sapporo
Hokkaido University
Takada, Ayato
Japan, Sapporo
Hokkaido University
Statistics
Citations: 28
Authors: 13
Affiliations: 5
Identifiers
Doi:
10.1371/journal.ppat.1004192
ISSN:
15537366
Research Areas
Maternal And Child Health