A Recombinant Vesicular Stomatitis Virus-Based Vaccine Provides Postexposure Protection Against Bundibugyo Ebolavirus Infection

J Infect Dis. 2023 Nov 15;228(Suppl 7):S712-S720. doi: 10.1093/infdis/jiad207.

Abstract

Background: The filovirus Bundibugyo virus (BDBV) causes severe disease with a mortality rate of approximately 20%-51%. The only licensed filovirus vaccine in the United States, Ervebo, consists of a recombinant vesicular stomatitis virus (rVSV) vector that expresses Ebola virus (EBOV) glycoprotein (GP). Ervebo was shown to rapidly protect against fatal Ebola disease in clinical trials; however, the vaccine is only indicated against EBOV. Recent outbreaks of other filoviruses underscore the need for additional vaccine candidates, particularly for BDBV infections.

Methods: To examine whether the rVSV vaccine candidate rVSVΔG/BDBV-GP could provide therapeutic protection against BDBV, we inoculated seven cynomolgus macaques with 1000 plaque-forming units of BDBV, administering rVSVΔG/BDBV-GP vaccine to 6 of them 20-23 minutes after infection.

Results: Five of the treated animals survived infection (83%) compared to an expected natural survival rate of 21% in this macaque model. All treated animals showed an early circulating immune response, while the untreated animal did not. Surviving animals showed evidence of both GP-specific IgM and IgG production, while animals that succumbed did not produce significant IgG.

Conclusions: This small, proof-of-concept study demonstrated early treatment with rVSVΔG/BDBV-GP provides a survival benefit in this nonhuman primate model of BDBV infection, perhaps through earlier initiation of adaptive immunity.

Keywords: Bundibugyo virus; Ervebo; ebolaviruses; filovirus; postexposure treatment; rVSVΔG/BDBV-GP; recombinant vesicular stomatitis virus; transcriptomics; vaccine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Viral
  • Ebola Vaccines*
  • Ebolavirus*
  • Glycoproteins / genetics
  • Hemorrhagic Fever, Ebola*
  • Immunoglobulin G
  • Macaca fascicularis
  • Vesicular Stomatitis* / prevention & control
  • Vesiculovirus / genetics
  • Viral Vaccines*

Substances

  • Antibodies, Viral
  • Glycoproteins
  • Viral Vaccines
  • Immunoglobulin G
  • Ebola Vaccines