title: Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.
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.
authors.affiliation: Laboratory of Virology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Marzi
authors.forename: Reiko
authors.initials: R
authors.lastname: Yoshida
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyamoto
authors.forename: Mari
authors.initials: M
authors.lastname: Ishijima
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Megumi
authors.initials: M
authors.lastname: Higuchi
authors.forename: Yukie
authors.initials: Y
authors.lastname: Matsuyama
authors.forename: Manabu
authors.initials: M
authors.lastname: Igarashi
authors.forename: Eri
authors.initials: E
authors.lastname: Nakayama
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuroda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saijo
authors.forename: Friederike
authors.initials: F
authors.lastname: Feldmann
authors.forename: Douglas
authors.initials: D
authors.lastname: Brining
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.forename: Ayato
authors.initials: A
authors.lastname: Takada
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology*; D000918:Antibody Specificity; D016466:CHO Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D000939:Epitopes / Q000276:immunology; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D006801:Humans; D007116:Immunization, Passive; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology; D014709:Vero Cells; D019562:Viral Load / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D011993:Recombinant Fusion Proteins