Protection against mucosal SHIV challenge by peptide and helper-dependent adenovirus vaccines

Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Stephanie J. Buchl, Donna Palmer, David C. Montefiori, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helperdependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5- immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than in the HD-Ad5 group. In this study, neutralizing antibody and T cell responses were compared between the groups before and after rectal challenge with CCR5-tropic SHIV-SF162P3. When serum samples were assayed for neutralizing antibodies, only weak activity was observed. T cell responses against env epitopes were higher in the serotype-switched group. When these animals were challenged rectally with SHIV-SF162P3, both the Ad5 and serotype-switch groups significantly reduced peak viral loads 2 to 10-fold 2 weeks after infection. Peak viral loads were significantly lower for the serotype-switched group as compared to the HD-Ad5-immunized group. Viral loads declined over 18 weeks after infection with some animals viremia reducing nearly 4 logs from the peak. These data demonstrate significant mucosal vaccine effects after immunization with only env antigens. These data also demonstrate HD-Ad vectors are a robust platform for vaccination.

Original languageEnglish (US)
Pages (from-to)920-938
Number of pages19
JournalViruses
Volume1
Issue number3
DOIs
StatePublished - Nov 10 2009

Keywords

  • Adenovirus
  • HIV-1
  • Helper-dependent vector
  • Mucosal challenge
  • SHIV
  • Serotype-switching

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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    Weaver, E. A., Nehete, P. N., Nehete, B. P., Buchl, S. J., Palmer, D., Montefiori, D. C., Ng, P., Jagannadha Sastry, K., & Barry, M. A. (2009). Protection against mucosal SHIV challenge by peptide and helper-dependent adenovirus vaccines. Viruses, 1(3), 920-938. https://doi.org/10.3390/v1030920