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Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses.
- Source :
-
Journal of acquired immune deficiency syndromes (1999) [J Acquir Immune Defic Syndr] 2015 Aug 01; Vol. 69 (4), pp. 385-94. - Publication Year :
- 2015
-
Abstract
- Background: Preexposure 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 Simian/Human Immunodeficiency Virus chimera (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.<br />Methods: 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 (TFV) K65R drug-resistant mutation (n = 12). PrEP consisted of oral Truvada (n = 6, WT), TFV vaginal gel (n = 6, K65R), or TFV intravaginal 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 interferon γ Enzyme-Linked ImmunoSpot (ELISPOT) and multiparameter flow cytometry.<br />Results: Of 9 animals that were on PrEP and remained uninfected during WT SHIV vaginal challenges, 8 (88.9%) developed virus-specific T-cell responses. T cells were in CD4 and CD8 compartments, reached up to 4900 interferon γ-producing cells per million peripheral blood mononuclear cells, 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.<br />Conclusions: 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 after PrEP warrants further investigation.
- Subjects :
- Administration, Oral
Administration, Topical
Animals
Drug Combinations
Drug Resistance, Viral
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Female
Pre-Exposure Prophylaxis
Reassortant Viruses drug effects
Simian Immunodeficiency Virus drug effects
Simian Immunodeficiency Virus immunology
Anti-HIV Agents therapeutic use
Deoxycytidine analogs & derivatives
HIV Infections prevention & control
Macaca nemestrina
Organophosphorus Compounds
Simian Acquired Immunodeficiency Syndrome prevention & control
T-Lymphocytes physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1944-7884
- Volume :
- 69
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of acquired immune deficiency syndromes (1999)
- Publication Type :
- Academic Journal
- Accession number :
- 25886925
- Full Text :
- https://doi.org/10.1097/QAI.0000000000000642