Title |
Protective Efficacy of Neutralizing Monoclonal Antibodies in a Nonhuman Primate Model of Ebola Hemorrhagic Fever
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Published in |
PLOS ONE, April 2012
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DOI | 10.1371/journal.pone.0036192 |
Pubmed ID | |
Authors |
Andrea Marzi, Reiko Yoshida, Hiroko Miyamoto, Mari Ishijima, Yasuhiko Suzuki, Megumi Higuchi, Yukie Matsuyama, Manabu Igarashi, Eri Nakayama, Makoto Kuroda, Masayuki Saijo, Friederike Feldmann, Douglas Brining, Heinz Feldmann, Ayato Takada |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Australia | 1 | 33% |
India | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 2% |
United Kingdom | 1 | <1% |
Australia | 1 | <1% |
Japan | 1 | <1% |
Canada | 1 | <1% |
Unknown | 105 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 30 | 27% |
Student > Bachelor | 18 | 16% |
Student > Ph. D. Student | 16 | 14% |
Student > Master | 11 | 10% |
Other | 10 | 9% |
Other | 16 | 14% |
Unknown | 10 | 9% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 36 | 32% |
Medicine and Dentistry | 17 | 15% |
Immunology and Microbiology | 12 | 11% |
Biochemistry, Genetics and Molecular Biology | 11 | 10% |
Nursing and Health Professions | 4 | 4% |
Other | 17 | 15% |
Unknown | 14 | 13% |