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

AIDS. 2018 Nov 13;32(17):2533-2545. doi: 10.1097/QAD.0000000000002026.


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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / administration & dosage*
  • Adult
  • Anti-Retroviral Agents / administration & dosage
  • Combined Modality Therapy / methods
  • Dendritic Cells / immunology*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • HIV Infections / therapy*
  • Humans
  • Male
  • Middle Aged
  • RNA, Messenger / administration & dosage*
  • Treatment Outcome


  • AIDS Vaccines
  • Anti-Retroviral Agents
  • RNA, Messenger

Associated data