Efficacy of Western, Eastern, and Venezuelan Equine Encephalitis (WEVEE) Virus-Replicon Particle (VRP) Vaccine against WEEV in a Non-Human Primate Animal Model

Viruses. 2022 Jul 8;14(7):1502. doi: 10.3390/v14071502.

Abstract

The purpose of this study was to evaluate the effects of the route of administration on the immunogenicity and efficacy of a combined western, eastern, and Venezuelan equine encephalitis (WEVEE) virus-like replicon particle (VRP) vaccine in cynomolgus macaques. The vaccine consisted of equal amounts of WEEV, EEEV, and VEEV VRPs. Thirty-three animals were randomly assigned to five treatment or control groups. Animals were vaccinated with two doses of WEVEE VRPs or the control 28 days apart. Blood was collected 28 days following primary vaccination and 21 days following boost vaccination for analysis of the immune response to the WEVEE VRP vaccine. NHPs were challenged by aerosol 28 or 29 days following second vaccination with WEEV CBA87. Vaccination with two doses of WEVEE VRP was immunogenic and resulted in neutralizing antibody responses specific for VEEV, EEEV and WEEV. None of the vaccinated animals met euthanasia criteria following aerosol exposure to WEEV CBA87. However, one NHP control (total of 11 controls) met euthanasia criteria after infection with WEEV CBA87. Statistically significant differences in median fever hours were noted in control NHPs compared to vaccinated NHPs, providing a quantitative measure of infection and efficacy of the vaccine against a WEEV challenge. Alterations in lymphocytes, monocytes, and neutrophils were observed. Lymphopenia was observed in control NHPs.

Keywords: Venezuelan equine encephalitis; alphavirus; eastern equine encephalitis; multi-agent vaccination; nonhuman primates; virus replicon particle; western equine encephalitis.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aerosols
  • Animals
  • Antibodies, Viral
  • Disease Models, Animal
  • Encephalitis Virus, Venezuelan Equine* / genetics
  • Encephalomyelitis, Venezuelan Equine* / prevention & control
  • Horses
  • Macaca fascicularis
  • Replicon
  • Viral Vaccines*

Substances

  • Aerosols
  • Antibodies, Viral
  • Viral Vaccines

Grants and funding

Funding for this effort was provided by the Medical Countermeasure Systems—Joint Vaccine Acquisition Program, within the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense’s [JPEO-CBRND] Joint Project Manager for Chemical, Biological, Radiological, and Nuclear Medical [JPM CBRN Medical], U.S. Department of Defense, under project number 1885296.