Phase I clinical trial of an intranodally administered mRNA-based therapeutic vaccine against HIV-1 infection.
AIDS
; 32(17): 2533-2545, 2018 11 13.
Article
en En
| MEDLINE
| ID: mdl-30289805
ABSTRACT
OBJECTIVE:
The efficacy of therapeutic vaccines against HIV-1 infection has been modest. New inerts to redirect responses to vulnerable sites are urgently needed to improve these results.DESIGN:
We performed the first-in-human clinical trial with naked mRNA (iHIVARNA) combining a dendritic cell activation strategy (TriMixCD40L+CD70+caTLR4 RNA) with a novel HIV immunogen sequences (HTI immunogen).METHODS:
A dose escalation, phase I clinical trial was performed in 21 chronic HIV-1-infected patients under ART who received three intranodal doses of mRNA (weeks 0, 2 and 4) as follow TriMix-100âg, TriMix-300âg, TriMix-300âg with HTI-300âg, TriMix-300âg with HTI-600âg, TriMix-300âg with HTI-900âg. Primary end-point was safety and secondary-exploratory end-points were immunogenicity, changes in viral reservoir and transcriptome.RESULTS:
Overall, the vaccine was secure and well tolerated. There were 31 grade 1/2 and 1 grade 3 adverse events, mostly unrelated to the vaccination. Patients who received the highest dose showed a moderate increase in T-cell responses spanning HTI sequence at week 8. In addition, the proportion of responders receiving any dose of HTI increased from 31% at w0 to 80% postvaccination. The intervention had no impact on caHIV-DNA levels, however, caHIV-RNA expression and usVL were transiently increased at weeks 5 and 6 in the highest dose of iHIVARNA, and these changes were positively correlated with HIV-1-specific-induced immune responses.CONCLUSION:
This phase I dose-escalating trial showed that iHIVARNA administration was safe and well tolerated, induced moderate HIV-specific T-cell responses and transiently increased different viral replication readouts. These data support further exploration of iHIVARNA in a phase II study. CLINICALTRIALS. GOV IDENTIFIER NCT02413645.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
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ARN Mensajero
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Infecciones por VIH
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Vacunas contra el SIDA
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
AIDS
Asunto de la revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Año:
2018
Tipo del documento:
Article