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

Leal, Lornaa,b; Guardo, Alberto C.b; Morón-López, Sarac; Salgado, Mariac; Mothe, Beatrizc; Heirman, Carlof; Pannus, Pieterg; Vanham, Guidog; Ham, Henk Jan van denh; Gruters, Robh; Andeweg, Arnoh; Van Meirvenne, Sonjaf; Pich, Juditb; Arnaiz, Joan Albertb; Gatell, Josep Ma,b; Brander, Christianc; Thielemans, Krisf; Martínez-Picado, Javierc,d,e; Plana, Montserratb; García, Felipea,b on behalf of the iHIVARNA consortium

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 DC 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 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.

Results: 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.

Conclusions: 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. Identifier: NCT02413645

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:

Received 4 April, 2018

Accepted 8 July, 2018

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