Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects

Introduction: Vaccines may be key components of a curative strategy for HIV-1. We investigated whether a novel immunogen, HIVconsv, designed to re-direct T cell responses to conserved viral epitopes, could impact the HIV-1 reservoir in chronic antiretroviral therapy (ART)-treated subjects when delivered by modified vaccinia virus Ankara (MVA). Methods: Nineteen virologically suppressed individuals were randomized to receive vaccinations with MVA. HIVconsv (5.5 x 10(7) plaque-forming units, pfu, n = 8; 2.2 x 10(8) pfu, n = 7) or placebo (n = 4) at 0, 4 and 12 weeks. Magnitude, breadth and antiviral function of vaccine-induced T cells, cell-associated HIV-1 DNA in circulating CD4+ T cells and residual viremia in plasma were measured before and after vaccination. Results: 90% of subjects completed the vaccine regimen; there were no serious vaccine-related adverse events. The magnitude of HIVconsv-specific IFN-gamma-secreting T cells was not significantly boosted in vaccinees when compared with placebos in ex vivo Elispot assays, due to greater than expected variation in HIV-specific T cell responses in the latter during the observation period. Ex vivo CD8+ T cell viral inhibitory capacity was modest but significantly increased post-vaccination with MVA. HIVconsv at the higher dose (p = 0.004) and was positively correlated with the frequency of HIVconsv-specific CD8 + CD107+ IFN-alpha +/- T cells (r = 0.57, p = 0.01). Total HIV-1 DNA and residual viral load did not change significantly from baseline in any group. Conclusions: Homologous prime-boost vaccination with MVA. HIVconsv was safe in HIV-positive ART-treated subjects but showed modest immunogenicity and did not significantly change the size of the viral reservoir. MVA. HIVconsv may be more effective when used in a heterologous prime-boost vaccination regimen and when combined with a latency-reversing agent.