Títol:
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Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects
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Autor/a:
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Hancock, Gemma; Moron-Lopez, Sara; Kopycinski, Jakub; Puertas, Maria C..; Giannoulatou, Eleni; Rose, Annie; Salgado, Maria; Hayton, Emma-Jo; Crook, Alison; Morgan, Catharine; Angus, Brian; Chen, Fabian; Yang, Hongbing; Martinez-Picado, Javier; Hanke, Tomáš; Dorrell, Lucy; Universitat Autònoma de Barcelona
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Abstract:
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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 × 10 7 plaque-forming units, pfu, n = 8; 2.2 × 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- 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 |
Matèries:
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-Human immunodeficiency virus -Therapeutic vaccine -Viral inhibition assay -Immunogen design -T cells -Conservation -MVA -Phase I trial |
Drets:
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open access
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Article |
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Uri:
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https://ddd.uab.cat/record/186251
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