Vesicular stomatitis virus-based Ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates

Thomas Geisbert, Kathleen M. Daddario-DiCaprio, Mark G. Lewis, Joan B. Geisbert, Allen Grolla, Anders Leung, Jason Paragas, Lennox Matthias, Mark A. Smith, Steven M. Jones, Lisa E. Hensley, Heinz Feldmann, Peter B. Jahrling

Research output: Contribution to journalArticle

132 Citations (Scopus)

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 (VSVDG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSVDG/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.

Original languageEnglish (US)
Article numbere1000225
JournalPLoS Pathogens
Volume4
Issue number11
DOIs
StatePublished - Nov 2008
Externally publishedYes

Fingerprint

Ebola Vaccines
Vesicular Stomatitis
Ebolavirus
Primates
Vaccines
HIV
Viruses
Simian Immunodeficiency Virus
Glycoproteins
Biological Warfare Agents
Central Africa
T-Lymphocytes
Democratic Republic of the Congo
Safety
Western Africa
Macaca
CD4 Lymphocyte Count
Macaca mulatta
Population
Disease Outbreaks

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Geisbert, T., Daddario-DiCaprio, K. M., Lewis, M. G., Geisbert, J. B., Grolla, A., Leung, A., ... Jahrling, P. B. (2008). Vesicular stomatitis virus-based Ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates. PLoS Pathogens, 4(11), [e1000225]. https://doi.org/10.1371/journal.ppat.1000225

Vesicular stomatitis virus-based Ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates. / Geisbert, Thomas; Daddario-DiCaprio, Kathleen M.; Lewis, Mark G.; Geisbert, Joan B.; Grolla, Allen; Leung, Anders; Paragas, Jason; Matthias, Lennox; Smith, Mark A.; Jones, Steven M.; Hensley, Lisa E.; Feldmann, Heinz; Jahrling, Peter B.

In: PLoS Pathogens, Vol. 4, No. 11, e1000225, 11.2008.

Research output: Contribution to journalArticle

Geisbert, T, Daddario-DiCaprio, KM, Lewis, MG, Geisbert, JB, Grolla, A, Leung, A, Paragas, J, Matthias, L, Smith, MA, Jones, SM, Hensley, LE, Feldmann, H & Jahrling, PB 2008, 'Vesicular stomatitis virus-based Ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates', PLoS Pathogens, vol. 4, no. 11, e1000225. https://doi.org/10.1371/journal.ppat.1000225
Geisbert, Thomas ; Daddario-DiCaprio, Kathleen M. ; Lewis, Mark G. ; Geisbert, Joan B. ; Grolla, Allen ; Leung, Anders ; Paragas, Jason ; Matthias, Lennox ; Smith, Mark A. ; Jones, Steven M. ; Hensley, Lisa E. ; Feldmann, Heinz ; Jahrling, Peter B. / Vesicular stomatitis virus-based Ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates. In: PLoS Pathogens. 2008 ; Vol. 4, No. 11.
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