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Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine
Nicole Frahm, … , Stephen C. De Rosa, M. Juliana McElrath
Nicole Frahm, … , Stephen C. De Rosa, M. Juliana McElrath
Published December 27, 2011
Citation Information: J Clin Invest. 2012;122(1):359-367. https://doi.org/10.1172/JCI60202.
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Research Article

Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine

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Abstract

Recombinant viruses hold promise as vectors for vaccines to prevent infectious diseases with significant global health impacts. One of their major limitations is that preexisting anti-vector neutralizing antibodies can reduce T cell responses to the insert antigens; however, the impact of vector-specific cellular immunity on subsequent insert-specific T cell responses has not been assessed in humans. Here, we have identified and compared adenovirus-specific and HIV-specific T cell responses in subjects participating in two HIV-1 vaccine trials using a vaccine vectored by adenovirus serotype 5 (Ad5). Higher frequencies of pre-immunization adenovirus-specific CD4+ T cells were associated with substantially decreased magnitude of HIV-specific CD4+ T cell responses and decreased breadth of HIV-specific CD8+ T cell responses in vaccine recipients, independent of type-specific preexisting Ad5-specific neutralizing antibody titers. Further, epitopes recognized by adenovirus-specific T cells were commonly conserved across many adenovirus serotypes, suggesting that cross-reactivity of preexisting adenovirus-specific T cells can extend to adenovirus vectors derived from rare serotypes. These findings provide what we believe to be a new understanding of how preexisting viral immunity may impact the efficacy of vaccines under current evaluation for prevention of HIV, tuberculosis, and malaria.

Authors

Nicole Frahm, Allan C. DeCamp, David P. Friedrich, Donald K. Carter, Olivier D. Defawe, James G. Kublin, Danilo R. Casimiro, Ann Duerr, Michael N. Robertson, Susan P. Buchbinder, Yunda Huang, Gregory A. Spies, Stephen C. De Rosa, M. Juliana McElrath

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Figure 4

Breadth and distribution of T cell responses to Ad5 15-mers.

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Breadth and distribution of T cell responses to Ad5 15-mers.
Responses t...
Responses to single Ad5 15-mer peptides were mapped by IFN-γ ELISPOT in 18 HVTN 071 vaccine recipients and 14 unvaccinated HIV-uninfected SACs. Breadth (A) and distribution (B) for each targeted 15-mer are shown for 13 HVTN 071 vaccinees (open squares) and 10 SACs (gray circles) with at least 1 positive response. Red bars represent medians. (A) Total breadth as measured by the number of targeted 15-mers across all tested proteins; two overlapping 15-mers were counted as a single response. (B) Number of targeted 15-mers per Ad5 protein (fiber generated no responses).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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