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

J Int AIDS Soc. 2017 May 19;20(1):21171. doi: 10.7448/IAS.20.1.21171.


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 × 107 plaque-forming units, pfu, n = 8; 2.2 × 108 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-γ-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-α± 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.

Clinical trials registration: NCT01024842.

Keywords: MVA; T cells; conservation; human immunodeficiency virus; immunogen design; phase I trial; therapeutic vaccine; viral inhibition assay.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Anti-HIV Agents / therapeutic use
  • Conserved Sequence / immunology
  • Double-Blind Method
  • Female
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV Infections / therapy*
  • HIV-1 / genetics
  • Humans
  • Immunogenicity, Vaccine*
  • Male
  • T-Lymphocytes / immunology
  • Vaccines, Synthetic / immunology
  • Vaccinia virus
  • Viral Load


  • AIDS Vaccines
  • Anti-HIV Agents
  • Vaccines, Synthetic

Associated data

  • ClinicalTrials.gov/NCT01024842