Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects
Hancock, Gemma
Moron-Lopez, Sara (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Kopycinski, Jakub
Puertas, Maria C.. (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Giannoulatou, Eleni (University of New South Wales)
Rose, Annie
Salgado, Maria (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Hayton, Emma-Jo
Crook, Alison
Morgan, Catharine
Angus, Brian
Chen, Fabian
Yang, Hongbing
Martinez-Picado, Javier (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Hanke, Tomáš
Dorrell, Lucy
Universitat Autònoma de Barcelona

Fecha:	2017
Resumen:	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.
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Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Human immunodeficiency virus ; Therapeutic vaccine ; Viral inhibition assay ; Immunogen design ; T cells ; Conservation ; MVA ; Phase I trial
Publicado en:	Journal of the International AIDS Society, Vol. 20 (may 2017) , ISSN 1758-2652

DOI: 10.7448/IAS.20.1.21171
PMID: 28537062

11 p, 1018.7 KB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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