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Title: iHIVARNA phase IIa, a randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy
Author: de Jong, Wesley
Aerts, Joeri
Gatell, José M.
Honrado, Ángel
Buyze, Jozefien
Florence, Eric
van Gorp, Eric
Van Meirvenne, Sonja
Leal, Lorna
Mothe, Beatriz
Thielemans, Kris
Heirman, Carlo
García Alcaide, Felipe
Gruters, Rob
Pannus, Pieter
Boers, Patrick
Arnaiz Gargallo, Juan Alberto
Plana Prades, Montserrat
Guardo, Alberto C.
Koopmans, Marion
Maleno, María José
Vanham, Guido
Lungu, Cynthia
Moltó, José
Salgado, Maria
Heyndrickx, Leo
Graupera, Anna
Scheuer, Rachel
Allard, Sabine
Tjok, Patrick
Brander, Christian
Martínez Picado, Javier
Olvera, Alex
Rosas Umbert, Miriam
Moron, Sara
Molto, Jose
López, Miriam
Keywords: Immunoteràpia
VIH (Virus)
HIV (Viruses)
Issue Date: 17-Jun-2019
Publisher: BioMed Central
Abstract: Background: HIV therapeutic vaccination aims to improve the immune responses against HIV in order to control viral replication without the need for combined antiretroviral therapy (cART). iHIVARNA-01 is a novel vaccine combining mRNA delivery and T-cell immunogen (HTI) based on conserved targets of effective antiviral T-cell responses. In addition, it holds adequate stimuli required for activating antigen presenting cells (APC)s and co-activating specific T-cells (TriMix), including human CD40L, constitutively active TLR4 (caTLR4) and CD70. We propose that in-vivo targeting of dendritic cells (DCs) by direct administration of a HIV mRNA encoding these immune modulating proteins might be an attractive alternative to target DCs in vitro. Methods/design: This is a phase-IIa, randomized, double-blinded, placebo-controlled, multicenter study in chronically HIV-1 infected patients under stable cART. One of the three study arms is randomly allocated to subjects. Three vaccinations with either HIVACAT T-cell immunogen (HTI)-TriMix (iHIVARNA-01), TriMix or water for injection (WFI) (weeks 0, 2 and 4) are administered by intranodal injection in the inguinal region. Two weeks after the last immunization (week 6) cART is stopped for 12 weeks. The two primary endpoints are: (1) safety and tolerability of intranodal iHIVARNA-01 vaccination compared with TriMix or WFI and (2) induced immunogenicity, i.e., increase in the frequency of HIV-specific T-cell responses between baseline, week 6 and 12 weeks after treatment interruption in iHIVARNA-01-treated patients as compared to the control groups, immunized with TriMix-mRNA or WFI measured by an IFNγ ELISPOT assay. Secondary endpoints include the evaluation of time to viral rebound, plasma viral load (pVL) at w18, the proportion of patients with control of viral load, induction of T-cell responses to new HIV epitopes, polyfunctionality of HIV-specific T-cells, CD8+ T-cell in-vitro HIV suppressive capacity, the effect on viral reservoir (measured by proviral DNA and cell-associated RNA), assessment of viral immune escape by mutation and mRNA expression profiles of host immune genes. Discussion: This trial aims to direct target DC in situ with mRNA encoding HTI and TriMix for co-stimulation. Intranodal injection circumvents laborious DC isolation and handling in the laboratory. The trial extends on the safety results of a phase-I dose-escalating trial. This candidate vaccine could complement or even replace cART for chronic HIV infection and could be applicable to improve the care and cost of HIV infection.
Note: Reproducció del document publicat a:
It is part of: Trials, 2019, vol. 20, num. 361
Related resource:
ISSN: 1745-6215
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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