Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 122, Issue 1, Pages 359-367Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI60202
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Funding
- NTH Division of AIDS
- Public Health Service [UM1 AI068618]
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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 (Ads). 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 Ads-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.
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