Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates

PLoS Pathogens

Peter B. Jahrling¹  Steven M. Jones¹  Mark G. Lewis²  Kathleen M. Daddario-DiCaprio³  Lennox Matthias⁴  Joan B. Geisbert⁴  Allen Grolla⁵  Lisa E. Hensley⁶  Jason Paragas⁶  Thomas W. Geisbert⁶  Anders Leung⁷  Mark A. Smith⁷  Heinz Feldmann⁷ 

[1] BIOQUAL, Rockville, Maryland, United States of America;Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America;Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America;Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America;Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America;National Emerging Infectious Diseases Laboratories Institute, Boston, Massachusetts, United States of America;Virology Division, BIOQUAL, Rockville, Maryland, United States of America

关键词: Macaque;    Vesicular stomatitis virus;    Vaccines;    Rhesus monkeys;    Vaccination;    immunization;    T cells;    Monkeys;    Viral vaccines;   

DOI  :  10.1371/journal.ppat.1000225

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV) is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVΔG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSVΔG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV.

【 授权许可】

CC BY