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.
We performed the first-in-human clinical trial with naked mRNA (iHIVARNA) combining a DC activation strategy (TriMix:CD40L+CD70+caTLR4 RNA) with a novel HIV immunogen sequences (HTI immunogen).
A dose escalation, phase I clinical trial was performed in 21 chronic HIV-1 infected patients under ART who received 3 intranodal doses of mRNA (weeks 0, 2 and 4) as follow: TriMix-100 g, TriMix-300 g, TriMix-300 g+HTI-300 g, TriMix-300 g+HTI-600 g, TriMix-300 g+HTI-900 g. Primary end-point was safety and secondary-exploratory end-points were immunogenicity, changes in viral reservoir and transcriptome.
Overall, the vaccine was safe 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% post-vaccination. 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.
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.
aInfectious Diseases Department, Hospital Clínic-HIVACAT, University of Barcelona, Barcelona, Spain
bInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-HIVACAT, Barcelona, Spain
cIrsiCaixa AIDS Research Institute – HIVACAT, Badalona, Spain
dUniversitat de Vic – Universitat Central de Catalunya (UVic-UCC), Spain
eCatalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain
fLaboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel (VUB), Brussels, Belgium
gVirology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
hDepartment of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
Correspondence to: Dr. Lorna Leal, MD, Infectious Diseases Unit, Hospital Clínic, Villarroel, 170, 08036 Barcelona, Spain. Tel: +34932275586; fax: +34934514438; e-mail: email@example.com
Received 4 April, 2018
Accepted 8 July, 2018
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