期刊
EBIOMEDICINE
卷 18, 期 -, 页码 204-215出版社
ELSEVIER
DOI: 10.1016/j.ebiom.2017.03.003
关键词
Heterologous viral vectored prime-boost immunization; Genetic adjuvant
资金
- Danish Research Council [060201464B]
- NIH [R01 AI084793]
- Danish AIDS-foundation [F10-18]
- Hede Nielsen Family Foundation [2012-1176]
- Foundation for the Advancement of Medical Sciences [90102]
- Aase and Ejnar Danielsen Foundation [106740]
- Novo Nordisk Foundation [12678]
- Lundbeck Foundation [R100-2011-9505] Funding Source: researchfish
Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-termcontrol. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, vif, rev and vpr antigens fused to the MHC class II associated invariant chain. Immunizations induced broad T cell responses in all vaccinees. Following up to 10 repeated low-dose intrarectal challenges, vaccinees suppressed early viral replication (P = 0.01) and prevented the peak viremia in 5/6 animals. Despite consistently undetectable viremia in 2 out of 6 vaccinees, all animals showed evidence of infection induced immune responses indicating that infection had taken place. Vaccinees, with and without detectable viremia better preserved their rectal CD4+ T cell population and had reduced immune hyperactivation asmeasured by naive T cell depletion, Ki-67 and PD-1 expression on T cells. These results indicate that vaccination towards SIV accessory antigens vaccine can provide a level of acute control of SIV replication with a suggestion of beneficial immunological consequences in infected animals of unknown long-term significance. In conclusion, our studies demonstrate that a vaccine encoding subdominant antigens not normally associated with virus control can exert a significant impact on acute peak viremia. (C) 2017 The Authors. Published by Elsevier B.V.
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