Comparison of Systemic and Mucosal Immunization withHelper-Dependent Adenoviruses for Vaccination against Mucosal Challenge with SHIV

Authors

Eric A. Weaver, Mayo ClinicFollow
Pramod N. Nehete, University of Texas M.D. Anderson Cancer Center
Bharti P. Nehete, University of Texas M.D. Anderson Cancer Center
Guojun Yang, University of Texas M.D. Anderson Cancer Center
Stephanie J. Buchl, University of Texas M.D. Anderson Cancer Center
Patrick W. Hanley, University of Texas M.D. Anderson Cancer Center, Houston
Donna Palmer, Baylor College of Medicine
David C. Montefiori, Duke University Medical Center
Guido Ferrari, Duke University Medical Center
Philip Ng, Baylor College of MedicineFollow
K. Jagannadha Sastry, University of Texas M.D. Anderson Cancer Center
Michael A. Barry, Mayo ClinicFollow

Date of this Version

7-3-2013

Citation

Weaver EA, Nehete PN, Nehete BP, Yang G, Buchl SJ, et al. (2013) Comparison of Systemic and Mucosal Immunization with Helper-Dependent Adenoviruses for Vaccination against Mucosal Challenge with SHIV. PLoS ONE 8(7): e67574. doi:10.1371/journal.pone.0067574

Comments

2013 Weaver et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Most HIV-1 infections are thought to occur at mucosal surfaces during sexual contact. It has been hypothesized that vaccines delivered at mucosal surfaces may mediate better protection against HIV-1 than vaccines that are delivered systemically. To test this, rhesus macaques were vaccinated by intramuscular (i.m.) or intravaginal (ivag.) routes with helperdependent adenoviral (HD-Ad) vectors expressing HIV-1 envelope. Macaques were first immunized intranasally with species C Ad serotype 5 (Ad5) prior to serotype-switching with species C HD-Ad6, Ad1, Ad5, and Ad2 vectors expressing env followed by rectal challenge with CCR5-tropic SHIV-SF162P3. Vaccination by the systemic route generated stronger systemic CD8 T cell responses in PBMC, but weaker mucosal responses. Conversely, mucosal immunization generated stronger CD4 T cell central memory (Tcm) responses in the colon. Intramuscular immunization generated higher levels of env-binding antibodies, but neither produced neutralizing or cytotoxic antibodies. After mucosal SHIV challenge, both groups controlled SHIV better than control animals. However, more animals in the ivag. group had lower viral set points than in in the i.m. group. These data suggest mucosal vaccination may have improve protection against sexually-transmitted HIV. These data also demonstrate that helper-dependent Ad vaccines can mediate robust vaccine responses in the face of prior immunity to Ad5 and during four rounds of adenovirus vaccination.