Vaccination of macaques with SIV immunogens delivered by Venezuelan equine encephalitis virus replicon particle vectors followed by a mucosal challenge with SIVsmE660

Robert E. Johnston, Philip R. Johnson, Mary J. Connell, David C. Montefiori, Ande West, Martha L. Collier, Chad Cecil, Ronald Swanstrom, Jeffrey A. Frelinger, Nancy L. Davis

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

VEE replicon particles (VRP), non-propagating vaccine vectors derived from Venezuelan equine encephalitis virus (VEE), were engineered to express immunogens from the cloned isolate SIVsmH-4, combined in a vaccine cocktail and inoculated subcutaneously to immunize rhesus macaques. The virulent, uncloned challenge stock, SIVsmE660, represented a type of heterologous challenge and the intrarectal challenge modeled infection across a mucosal surface. Prechallenge neutralizing antibodies against SIVsmH-4 were induced in all vaccinates, and a prechallenge cellular immune response could be detected in one of six. Post-challenge, virus loads were reduced at the peak, at set point and at termination (41 weeks post-challenge), although these differences did not reach statistical significance. Significantly elevated levels of CD4+ T cells were observed post-challenge. A strong correlation was noted between a net increase in CD4+ T cell count and lowered virus load at set point.

Original languageEnglish (US)
Pages (from-to)4969-4979
Number of pages11
JournalVaccine
Volume23
Issue number42
DOIs
StatePublished - Oct 10 2005
Externally publishedYes

Keywords

  • Replicon
  • SIV
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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    Johnston, R. E., Johnson, P. R., Connell, M. J., Montefiori, D. C., West, A., Collier, M. L., Cecil, C., Swanstrom, R., Frelinger, J. A., & Davis, N. L. (2005). Vaccination of macaques with SIV immunogens delivered by Venezuelan equine encephalitis virus replicon particle vectors followed by a mucosal challenge with SIVsmE660. Vaccine, 23(42), 4969-4979. https://doi.org/10.1016/j.vaccine.2005.05.034