Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 11, Issue 519, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aav1800
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Funding
- NIH [PO1 AI088575, U19AI096187, UM1 AI124436]
- Emory University CFAR [P30 AI050409]
- NCRR/NIH [P30 RR00165, P51OD01425, P30 RR00168]
- NCRR/NIH [NIAID] [HHSN272201300010C]
- Division of Intramural Research, NIAID, NIH
- Simian Vaccine Evaluation Unit of the Division of AIDS, NIAID
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Activated CD4 T cells are a major target of HIV infection. Results from the STEP HIV vaccine trial highlighted a potential role for total activated CD4T cells in promoting HIV acquisition. However, the influence of vaccine insert-specific CD4 T cell responses on HIV acquisition is not known. Here, using the data obtained from four macaque studies, we show that the DNA prime/modified vaccinia Ankara boost vaccine induced interferon gamma (IFN gamma(+)) CD4 T cells [T helper 1 (T(H)1) cells] rapidly migrate to multiple tissues including colon, cervix, and vaginal mucosa. These mucosal T(H)1 cells persisted at higher frequencies and expressed higher density of CCR5, a viral coreceptor, compared to cells in blood. After intravaginal or intrarectal simian immunodeficiency virus (SIV)/simian-human immunodeficiency virus (SHIV) challenges, strong vaccine protection was evident only in animals that had lower frequencies of vaccine-specific T(H)1 cells but not in animals that had higher frequencies of T(H)1 cells, despite comparable vaccine-induced humoral and CD8 T cell immunity in both groups. An RNA transcriptome signature in blood at 7 days after priming immunization from one study was associated with induction of fewer T(H)1-type CD4 cells and enhanced protection. These results demonstrate that high and persisting frequencies of HIV vaccine-induced T(H)1-biased CD4 T cells in the intestinal and genital mucosa can mitigate beneficial effects of protective antibodies and CD8 T cells, highlighting a critical role of priming immunization and vaccine adjuvants in modulating HIV vaccine efficacy.
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