Dataset Information

Phase I clinical trial of an intranodally administered mRNA-based therapeutic vaccine against HIV-1 infection.

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 (TriMix:CD40L+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-100?g, TriMix-300?g, TriMix-300?g with HTI-300?g, TriMix-300?g with HTI-600?g, TriMix-300?g with HTI-900?g. 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.

SUBMITTER: Leal L

PROVIDER: S-EPMC6221380 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Phase I clinical trial of an intranodally administered mRNA-based therapeutic vaccine against HIV-1 infection.

Leal Lorna L Guardo Alberto C AC Morón-López Sara S Salgado Maria M Mothe Beatriz B Heirman Carlo C Pannus Pieter P Vanham Guido G van den Ham Henk Jan HJ Gruters Rob R Andeweg Arno A Van Meirvenne Sonja S Pich Judit J Arnaiz Joan Albert JA Gatell Josep M JM Brander Christian C Thielemans Kris K Martínez-Picado Javier J Plana Montserrat M García Felipe F

AIDS (London, England) 20181101 17

<h4>Objective</h4>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.<h4>Design</h4>We performed the first-in-human clinical trial with naked mRNA (iHIVARNA) combining a dendritic cell activation strategy (TriMix:CD40L+CD70+caTLR4 RNA) with a novel HIV immunogen sequences (HTI immunogen).<h4>Methods</h4>A dose escalation, phase I clinical trial was performed in 21 chronic ...[more]

PMID: 30289805

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Dataset Information

Phase I clinical trial of an intranodally administered mRNA-based therapeutic vaccine against HIV-1 infection.

Objective

Design

Methods

Results

Conclusion

Gov identifier

Publications

Phase I clinical trial of an intranodally administered mRNA-based therapeutic vaccine against HIV-1 infection.

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