| 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. |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/59414 |
| 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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