Repeated vaginal SHIV challenges in macaques receiving oral or topical Pre-Exposure Prophylaxis induce virus-specific T cell responses

Details

• Alternative Title:
  J Acquir Immune Defic Syndr
• Personal Author:
  Tsegaye, Theodros Solomon ; Butler, Katherine ; Luo, Wei ; Radzio, Jessica ; Srinivasan, Priya ; Sharma, Sunita ; Aubert, Rachael D. ; Hanson, Debra L. ; Dobard, Charles ; Garcia-Lerma, J. Gerardo ; Heneine, Walid ; McNicholl, Janet M. ; Kersh, Ellen N.
• Description:
  Background
  
  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.
  
  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 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.
  
  Results
  
  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.
  
  Conclusion
  
  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.
  
  
• Subjects:
  Administration, Oral Administration, Topical Animals Anti-HIV Agents Deoxycytidine Drug Combinations Drug Resistance, Viral Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination Female HIV Infections Macaca Nemestrina Organophosphorus Compounds Pre-Exposure Prophylaxis Reassortant Viruses Simian Acquired Immunodeficiency Syndrome Simian Immunodeficiency Virus T-Lymphocytes

  More +
• Keywords:
  Exposed Uninfected Pig Tail Macaques Pre-exposure Prophylaxis SHIV T Cell Immune Response
• Source:
  J Acquir Immune Defic Syndr. 69(4):385-394
• Pubmed ID:
  25886925
• Pubmed Central ID:
  PMC4485592
• Document Type:
  Journal Article
• Funding:
  CC999999/Intramural CDC HHSUnited States/ ; Y01 AI000681/AI/NIAID NIH HHSUnited States/ ; Y01 AI000681-02/AI/NIAID NIH HHSUnited States/ ; Y1-AI-0681-02/AI/NIAID NIH HHSUnited States/
• Volume:
  69
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:63d63cc64a1f1ddc6b21f4c023fc2cbb594353ef756aec00e403d447217ff18a
• Download URL:
  https://stacks.cdc.gov/view/cdc/31881/cdc_31881_DS1.pdf
• File Type:
  [PDF - 2.13 MB ]