title: Vesicular stomatitis virus-based ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates.
abstract: 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 (VSVDeltaG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSVDeltaG/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.
authors.affiliation: National Emerging Infectious Diseases Laboratories Institute, Boston, Massachusetts, USA. geisbert@bu.edu
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Daddario-Dicaprio
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Joan B
authors.initials: JB
authors.lastname: Geisbert
authors.forename: Allen
authors.initials: A
authors.lastname: Grolla
authors.forename: Anders
authors.initials: A
authors.lastname: Leung
authors.forename: Jason
authors.initials: J
authors.lastname: Paragas
authors.forename: Lennox
authors.initials: L
authors.lastname: Matthias
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Steven M
authors.initials: SM
authors.lastname: Jones
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D046129:Ebola Vaccines / Q000008:administration & dosage / Q000494:pharmacology*; D005822:Genetic Vectors; D016867:Immunocompromised Host; D008253:Macaca mulatta; D011323:Primates; D016097:Simian Acquired Immunodeficiency Syndrome / Q000628:therapy; D016896:Treatment Outcome; D054243:Vesicular Stomatitis; D014764:Viral Proteins
chemical_list: D046129:Ebola Vaccines; D014764:Viral Proteins