Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines

Authors

Eric A. Weaver, University of Nebraska-LincolnFollow
Pramod N. Nehete, The University of Texas, Bastrop
Bharti P. Nehete, The University of Texas, Bastrop
Stephanie J. Buchl, The University of Texas, Bastrop
Donna Palmer, Baylor College of Medicine, Houston
David C. Montefiori, Baylor College of Medicine, Houston
Philip Ng, Baylor College of Medicine, HoustonFollow
K. Jagannadha Sastry, The University of Texas, Bastrop & The University of Texas, Houston
Michael A. Barry, Mayo Clinic, RochesterFollow

Document Type

Article

Date of this Version

10-10-2009

Citation

2009 by the authors

doi:10.3390/v1030920

Comments

Viruses 2009, 1, 920-938

www.mdpi.com/journal/viruses

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.