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Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines
Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology Program, Mayo Clinic, Rochester, MN 55905, USA
Department of Veterinary Sciences, M.D. Anderson Cancer Center, The University of Texas, Bastrop, TX 78602, USA
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Duke University Medical Center, Durham, NC 27710, USA
Department of Immunology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX 77054, USA
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA
Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 5 October 2009; in revised form: 6 November 2009 / Accepted: 9 November 2009 / Published: 10 November 2009
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.
Keywords: HIV-1; SHIV; adenovirus; helper-dependent vector; mucosal challenge; serotype-switching
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Weaver, E.A.; Nehete, P.N.; Nehete, B.P.; Buchl, S.J.; Palmer, D.; Montefiori, D.C.; Ng, P.; Sastry, K.J.; Barry, M.A. Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines. Viruses 2009, 1, 920-938.
Weaver EA, Nehete PN, Nehete BP, Buchl SJ, Palmer D, Montefiori DC, Ng P, Sastry KJ, Barry MA. Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines. Viruses. 2009; 1(3):920-938.
Weaver, Eric A.; Nehete, Pramod N.; Nehete, Bharti P.; Buchl, Stephanie J.; Palmer, Donna; Montefiori, David C.; Ng, Philip; Sastry, K. Jagannadha; Barry, Michael A. 2009. "Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines." Viruses 1, no. 3: 920-938.