Repeated vaginal SHIV challenges in macaques receiving oral or topical Pre-Exposure Prophylaxis induce virus-specific T cell responses
Published Date:Aug 1 2015
Source:J Acquir Immune Defic Syndr. 69(4):385-394.
Drug Resistance, Viral
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Pig Tail Macaques
Simian Acquired Immunodeficiency Syndrome
Simian Immunodeficiency Virus
T Cell Immune Response
Pubmed Central ID:PMC4485592
Funding:CC999999/Intramural CDC HHS/United States
Y01 AI000681-02/AI/NIAID NIH HHS/United States
Y1-AI-0681-02/AI/NIAID NIH HHS/United States
Pre-Exposure Prophylaxis (PrEP) for HIV prevention is a novel biomedical prevention method. We have previously modeled PrEP during rectal SHIV exposures in macaques and identified that SHIV-specific T cell responses were induced in the presence of antiretroviral drugs, an observation previously termed T cell chemo-vaccination. This report expands those initial findings by examining a larger group of macaques that were given oral or topical PrEP during repeated vaginal virus exposure.
Thirty-six female pigtail macaques received up to 20 repeat low-dose vaginal inoculations with wild type (WT) SHIVSF162P3 (n=24) or a clonal derivative with the tenofovir K65R drug resistant mutation (n=12). PrEP consisted of oral Truvada (n=6, WT), tenofovir vaginal gel (n=6, K65R), or tenofovir intra-vaginal ring (n=6, WT). The remaining animals were PrEP-inexperienced controls (n=12, WT; n=6, K65R). SHIV-specific T cells were identified and characterized using IFNγ ELISPOT and multi-parameter flow cytometry.
Of nine animals that were on PrEP and remained uninfected during WT SHIV vaginal challenges, eight (88.9%) developed virus-specific T cell responses. T cells were in CD4 and CD8 compartments, reached up to 4,900 IFNγ producing cells per million PBMCs, and primarily pol directed. In contrast, the replication impaired K65R virus did not induce detectable T cell responses, likely reflecting the need for adequate replication.
Virus-specific T cell responses occur frequently in oral or topical PrEP-protected pigtail macaques after vaginal exposure to WT SHIV virus. The contribution of such immune responses to protection from infection during and following PrEP warrants further investigation.
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