期刊
JOURNAL OF IMMUNOLOGY
卷 190, 期 6, 页码 2720-2735出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1202861
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资金
- Foundation for the National Institutes of Health
- Collaboration for AIDS Vaccine Discovery Award rom the Bill and Melinda Gates Foundation [OPP1039775]
- Bill and Melinda Gates Foundation [OPP1039775] Funding Source: Bill and Melinda Gates Foundation
- Wellcome Trust [100326/Z/12/Z] Funding Source: researchfish
Recombinant adenoviral vectors (rAds) are the most potent recombinant vaccines for eliciting CD8(+) T cell-mediated immunity in humans; however, prior exposure from natural adenoviral infection can decrease such responses. In this study we show low seroreactivity in humans against simian-(sAd11, sAd16) or chimpanzee-derived (chAd3, chAd63) compared with human-derived (rAd5, rAd28, rAd35) vectors across multiple geographic regions. We then compared the magnitude, quality, phenotype, and protective capacity of CD8(+) T cell responses in mice vaccinated with rAds encoding SIV Gag. Using a dose range (1 x 10(7)-10(9) particle units), we defined a hierarchy among rAd vectors based on the magnitude and protective capacity of CD8(+) T cell responses, from most to least, as: rAd5 and chAd3, rAd28 and sAd11, chAd63, sAd16, and rAd35. Selection of rAd vector or dose could modulate the proportion and/or frequency of IFN-gamma+TNF-alpha+IL-2(+) and KLRG1(+)CD127(-)CD8(+) T cells, but strikingly similar to 30-80% of memory CD8(+) T cells coexpressed CD127 and KLRG1. To further optimize CD8(+) T cell responses, we assessed rAds as part of prime-boost regimens. Mice primed with rAds and boosted with NYVAC generated Gag-specific responses that approached similar to 60% of total CD8(+) T cells at peak. Alternatively, priming with DNA or rAd28 and boosting with rAd5 or chAd3 induced robust and equivalent CD8(+) T cell responses compared with prime or boost alone. Collectively, these data provide the immunologic basis for using specific rAd vectors alone or as part of prime-boost regimens to induce CD8(+) T cells for rapid effector function or robust long-term memory, respectively. The Journal of Immunology, 2013, 190: 2720-2735.
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