Neutralizing Antibody Fails to Impact the Course of Ebola Virus Infection in Monkeys

PLoS Pathogens

Dennis R Burton¹  Paul W. H. I Parren¹  Wendelien B Oswald¹  Peter B Jahrling²  Joan B Geisbert²  Thomas W Geisbert²  Kelly J Davis²  Nancy J Sullivan³ 

[1] Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America;United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America;Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America

关键词: Antibodies;    Macaque;    Monkeys;    Enzyme-linked immunoassays;    Immunohistochemistry techniques;    Ebola virus;    Monoclonal antibodies;    Rhesus monkeys;   

DOI  :  10.1371/journal.ppat.0030009

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge. A control animal was exposed to virus in the absence of antibody treatment. Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection. We show that the inability of antibody to impact infection was not due to neutralization escape. It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody.

【 授权许可】

CC BY