期刊
JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
卷 20, 期 -, 页码 -出版社
JOHN WILEY & SONS LTD
DOI: 10.7448/IAS.20.1.21171
关键词
human immunodeficiency virus; therapeutic vaccine; viral inhibition assay; immunogen design; T cells; conservation; MVA; phase I trial
资金
- UK Medical Research Council [G0502048]
- UK Department for International Development (DFID) under MRC/DFID
- Oxford NIHR Biomedical Research Centre
- MRC [G1001757, G0502048, MR/N023668/1, MC_U137884179, G0701669] Funding Source: UKRI
- Medical Research Council [MR/N023668/1, MC_U137884179, G0502048, G0701669, G1001757] Funding Source: researchfish
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.
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