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

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

Online publication: 26/06/2017 Journal: Journal of the International AIDS Society

Abstract:

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 × 107plaque-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.

Authors: Hancock G, Morón-López S, Kopycinski J, Puertas MC, Giannoulatou E, Rose A, Salgado M, Hayton EJ, Crook A, Morgan C, Angus B, Chen F, Yang H, Martinez-Picado J, Hanke T, Dorrell L

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