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Viruses 2009, 1(3), 920-938; doi:10.3390/v1030920
Article

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

1,#, 2,#, 2, 2, 3, 4, 3, 2,5 and 1,6,7,*
1 Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology Program, Mayo Clinic, Rochester, MN 55905, USA 2 Department of Veterinary Sciences, M.D. Anderson Cancer Center, The University of Texas, Bastrop, TX 78602, USA 3 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA 4 Duke University Medical Center, Durham, NC 27710, USA 5 Department of Immunology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX 77054, USA 6 Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA 7 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 / Revised: 6 November 2009 / Accepted: 9 November 2009 / Published: 10 November 2009
(This article belongs to the Special Issue AIDS Vaccine)
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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 HIV-1; SHIV; adenovirus; helper-dependent vector; mucosal challenge; serotype-switching
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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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.

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