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Protective Efficacy of Neutralizing Monoclonal Antibodies in a Nonhuman Primate Model of Ebola Hemorrhagic Fever

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Title: Protective Efficacy of Neutralizing Monoclonal Antibodies in a Nonhuman Primate Model of Ebola Hemorrhagic Fever
Authors: Marzi, Andrea Browse this author
Yoshida, Reiko Browse this author →KAKEN DB
Miyamoto, Hiroko Browse this author
Ishijima, Mari Browse this author
Suzuki, Yasuhiko Browse this author →KAKEN DB
Higuchi, Megumi Browse this author
Matsuyama, Yukie Browse this author
Igarashi, Manabu Browse this author →KAKEN DB
Nakayama, Eri Browse this author
Kuroda, Makoto Browse this author
Saijo, Masayuki Browse this author →KAKEN DB
Feldmann, Friederike Browse this author
Brining, Douglas Browse this author
Feldmann, Heinz Browse this author
Takada, Ayato Browse this author →KAKEN DB
Issue Date: 27-Apr-2012
Publisher: The Public Library of Science
Journal Title: PLoS ONE
Volume: 7
Issue: 4
Start Page: e36192
Publisher DOI: 10.1371/journal.pone.0036192
Abstract: Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.
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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