OA17.06
Background: HVTN076 is an exploratory vaccine trial examining mucosal immune responses to the NIH Vaccine Research Center multiclade HIV-1 DNA/rAd5 vaccine, also used in the HVTN505 test-of-concept study.
Methods: 17 healthy Ad5 seronegative HIV-uninfected adults enrolled; 16 completed all vaccinations (3xDNA, rAd5; 0, 4, 8, 24 wks). Mucosal biopsies were obtained from sigmoid colon and rectum by flexible sigmoidoscopy at baseline and 1 month after rAd5. Rectal biopsies by anoscopy were obtained 2 weeks after final DNA and 1 week after rAd5. Single-cell suspensions following collagenase digestion were assayed directly for phenotyping and after overnight rest for intracellular cytokine staining. HIV-specific IgG was measured in serum and mucosal secretions.
Results: HIV-specific CD4+ and CD8+ T cells were detected in blood at 1 month post rAd5 (69 and 44% of participants for Gag, respectively), but none were detected in colon/rectum samples at any timepoint. Ad-specific CD4+ T cells, measured in response to the hexon coat protein, were detected at baseline in blood (92%) and colon (87%). Hexon-specific response rate and magnitude increased in blood after vaccination, but this increase was less common in colon/rectum. The proportion of CD4+ T cells expressing CCR5 or activated CD4+ T cells (Ki-67+BcL-2lo) in the rectum was unchanged after rAd5 vaccination. Env-specific IgG was detected in serum and mucosal secretions.
Conclusions: The vaccine regimen did not induce detectable HIV-specific T cells in colonic/rectal mucosa, an important site for HIV acquisition. These cells may be present, but require in vitro expansion for detection. Pre-existing mucosal Ad-specific T cells were detected in the majority of these Ad5 seronegatives. Activation of such cells is a potential concern for enhanced risk of HIV infection after rAd5 vaccination; however, post-vaccination increase in Ad-specific T cells was detected in few vaccines. Vaccine-induced activation of T cells in bulk, as measured by Ki-67/BcL-2, was not detected.
