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

Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Guojun Yang, Stephanie J. Buchl, Patrick W. Hanley, Donna Palmer, David C. Montefiori, Guido Ferrari, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 helper-dependent 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.

Original languageEnglish (US)
Article numbere67574
JournalPloS one
Volume8
Issue number7
DOIs
StatePublished - Jul 3 2013

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Immunization
Adenoviridae
immunization
serotypes
Vaccination
Vaccines
Human immunodeficiency virus 1
vaccination
vaccines
HIV-1
T-cells
Animals
T-lymphocytes
T-Lymphocytes
Tropics
AIDS Vaccines
antibodies
Antibodies
Macaca
mononuclear leukocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Comparison of Systemic and Mucosal Immunization with Helper-Dependent Adenoviruses for Vaccination against Mucosal Challenge with SHIV. / Weaver, Eric A.; Nehete, Pramod N.; Nehete, Bharti P.; Yang, Guojun; Buchl, Stephanie J.; Hanley, Patrick W.; Palmer, Donna; Montefiori, David C.; Ferrari, Guido; Ng, Philip; Sastry, K. Jagannadha; Barry, Michael A.

In: PloS one, Vol. 8, No. 7, e67574, 03.07.2013.

Research output: Contribution to journalArticle

Weaver, EA, Nehete, PN, Nehete, BP, Yang, G, Buchl, SJ, Hanley, PW, Palmer, D, Montefiori, DC, Ferrari, G, Ng, P, Sastry, KJ & Barry, MA 2013, 'Comparison of Systemic and Mucosal Immunization with Helper-Dependent Adenoviruses for Vaccination against Mucosal Challenge with SHIV', PloS one, vol. 8, no. 7, e67574. https://doi.org/10.1371/journal.pone.0067574
Weaver, Eric A. ; Nehete, Pramod N. ; Nehete, Bharti P. ; Yang, Guojun ; Buchl, Stephanie J. ; Hanley, Patrick W. ; Palmer, Donna ; Montefiori, David C. ; Ferrari, Guido ; Ng, Philip ; Sastry, K. Jagannadha ; Barry, Michael A. / Comparison of Systemic and Mucosal Immunization with Helper-Dependent Adenoviruses for Vaccination against Mucosal Challenge with SHIV. In: PloS one. 2013 ; Vol. 8, No. 7.
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