Safety, immunogenicity and effect on viral rebound of HTI vaccines combined with a TLR7 agonist in early-treated HIV-1 infection: a randomized, placebo-controlled phase 2a trial.

Yanhui Cai, Paula Suanzes, Carmen Busca, Leire Pérez-Latorre, Lucio Jesús García-Fraile, Gina Mejía-Abril, Jose M Miró, Sofía Scévola, Michelle Frankot, Daina Lim, Susana Benet, Elena Vendrame, Jeffrey J Wallin, Romas Geleziunas, Devi SenGupta, Yovaninna Alarcón-Soto, Alvaro Aranguen, Margarida Garcia-Garcia, Jose Ramón Arribas, Ignacio de Los Santos, Susan Guo, Jordi Navarro, Beatriz Mothe, Santiago Moreno, Adrian Curran, Arkaitz Imaz, Christian Brander, Ian McGowan, José Moltó, Isabel Leal, Juan Ambrosioni, Yuan Tian, Pere Domingo, Juan Berenguer, Juan González-García, Lucia Bailón, Julen Cadiñanos, Juan Carlos Lopez Bernaldo de Quirós

Journal: Nature communications 2025;16(1):2146

PMID: 40038256

Free Full Text on Nature Publishing Group View on PubMed

Abstract

Building on results from the AELIX-002 trial with HIVACAT T-cell immunogen (HTI)-based vaccines, the AELIX-003 (NCT04364035) trial tested the safety of the combination of ChAdOx1.HTI (C) and MVA.HTI (M), with the TLR7 agonist vesatolimod (VES), in a double-blind, placebo-controlled, randomized clinical trial in 50 virally suppressed early-treated men with HIV-1 infection. Secondary objectives included immunogenicity and effects on viral rebound kinetics during a 24-week antiretroviral treatment interruption (ATI). The most common treatment-related adverse events were mild-to-moderate injection-site pain, influenza-like illness, headache, and fatigue. Strong, broad, and HTI-focused T-cell responses were induced by vaccination. All participants experienced viral rebound in ATI; 33.3% and 23.5% (P = 0.4494) of CCMM + VES and placebo recipients, respectively, remained off antiretroviral therapy for 24 weeks. Post hoc analysis confirmed a correlation between levels of HTI-specific T cells and prolonged time off antiretroviral therapy. The combination of HTI vaccines and VES was safe and elicited robust T-cell responses.

Address: Department of Infectious Diseases and Fundació Lluita contra les Infeccions, Hospital Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain.; Department of Medicine, Autonomous University of Barcelona, Cerdanyola del Vallés, Spain.; Department of Infectious Diseases and Fundació Lluita contra les Infeccions, Hospital Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain.; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.; Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.; Hospital Universitario La Paz, Madrid, Spain.; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.; Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.; Hospital Universitario de la Princesa, Madrid, Spain.; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.; HIV Unit, Infectious Diseases Service, Hospital Clinic-Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), University of Barcelona, Barcelona, Spain.; HIV and STI Unit. Department of Infectious Diseases. Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, L'Hospitalet de Llobregat, Spain.; Department of Infectious Diseases and Fundació Lluita contra les Infeccions, Hospital Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain.; Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.; Hospital Universitario de la Princesa, Madrid, Spain.; Hospital Universitario Ramón y Cajal, Alcalá University, IRYCIS, Madrid, Spain.; Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.; Gilead Sciences, Inc, Foster City, CA, USA.; ClinData Insight, Inc, Moraga, CA, USA.; AELIX Therapeutics S.L, Barcelona, Spain.; AELIX Therapeutics S.L, Barcelona, Spain.; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain. [email protected].; AELIX Therapeutics S.L, Barcelona, Spain. [email protected].; IrsiCaixa, Hospital Universitari Germans Trias I Pujol, Barcelona, Spain. [email protected].; Department of Infectious Diseases and Immunity, University of Vic - Central University of Catalonia (UVic-UCC), Vic, Spain. [email protected].; ICREA, Barcelona, Spain. [email protected].; Department of Infectious Diseases and Fundació Lluita contra les Infeccions, Hospital Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain. [email protected].; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain. [email protected].; IrsiCaixa, Hospital Universitari Germans Trias I Pujol, Barcelona, Spain. [email protected].; Department of Infectious Diseases and Immunity, University of Vic - Central University of Catalonia (UVic-UCC), Vic, Spain. [email protected].

DOI: 10.1038/s41467-025-57284-w

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MeSH Terms: Humans, HIV Infections, Male, Toll-Like Receptor 7, HIV-1, Adult, AIDS Vaccines, Double-Blind Method, Middle Aged, Viral Load, Immunogenicity, Vaccine, Pteridines