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
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.
Authors
- Leire Pérez‐Latorre (ORCID: https://orcid.org/0000-0001-9919-3778)
- Alberto Manuel Borobia (ORCID: https://orcid.org/0000-0002-8584-3263)
- Yuan Tian (ORCID: https://orcid.org/0000-0002-2296-1246)
- José Moltó (ORCID: https://orcid.org/0000-0003-4564-1963)
- Isabel Maria Pereira Leal (ORCID: https://orcid.org/0000-0002-1672-7912)
- Benito García (ORCID: https://orcid.org/0000-0003-1320-5227)
- Enrique Seco
- Adrián Curran (ORCID: https://orcid.org/0000-0002-1263-0814)
- Ian McGowan (ORCID: https://orcid.org/0000-0002-6470-8476)
- Irene Soriano
- Sandra Morenilla
- Judith Grau-Expósito (ORCID: https://orcid.org/0000-0001-9350-2429)
- Víctor Hontañón (ORCID: https://orcid.org/0000-0003-3070-2647)
- J. M. Serra
- Patricia Cobarsí
- Lucía Bailón (ORCID: https://orcid.org/0000-0001-7277-9314)
- Samandhy Cedeño (ORCID: https://orcid.org/0000-0001-8312-0208)
- Bonaventura Clotet (ORCID: https://orcid.org/0000-0003-3232-4598)
- Paula Suanzes (ORCID: https://orcid.org/0000-0002-6871-0098)
- Ignacio de los Santos (ORCID: https://orcid.org/0000-0001-7073-5211)
- Sofía Scévola (ORCID: https://orcid.org/0000-0003-3578-5031)
- Eva Ariza
- José Ramón Arribas (ORCID: https://orcid.org/0000-0002-7410-9450)
- Devi SenGupta (ORCID: https://orcid.org/0000-0003-3811-8111)
- Yanhui Cai (ORCID: https://orcid.org/0009-0001-9936-8184)
- Alejandro de Miguel‐Cáceres (ORCID: https://orcid.org/0000-0002-2963-1573)
- Daniel Vázquez
- Juan Berenguer (ORCID: https://orcid.org/0000-0001-8541-8200)
- Juan Ambrosioni (ORCID: https://orcid.org/0000-0001-9931-6686)
- Francisco A. Perez (ORCID: https://orcid.org/0000-0001-8456-5209)
- Beatriz Mothe (ORCID: https://orcid.org/0000-0001-9975-407X)
- Joaquín Burgos (ORCID: https://orcid.org/0000-0001-8445-3047)
- Arkaitz Imaz (ORCID: https://orcid.org/0000-0001-8411-1952)
- Paloma Gijón (ORCID: https://orcid.org/0000-0002-5011-1927)
- María Luz García‐García (ORCID: https://orcid.org/0000-0003-4906-4227)
- Gina Mejía‐Abril (ORCID: https://orcid.org/0000-0002-8689-7941)
- Carmen Busca
- María J. Buzón (ORCID: https://orcid.org/0000-0003-4427-9413)
- Jordi Naval
- Jeffrey J. Wallin (ORCID: https://orcid.org/0000-0002-5952-3813)
- Jordi Puig (ORCID: https://orcid.org/0000-0002-4075-0346)
- Yovaninna Alarcón‐Soto (ORCID: https://orcid.org/0000-0002-9977-8634)
- Julen Cadiñanos (ORCID: https://orcid.org/0000-0003-1555-1668)
- Jordí Niubó (ORCID: https://orcid.org/0000-0001-9511-0138)
- Vicenç Falcó (ORCID: https://orcid.org/0000-0001-9626-0023)
- J. Cabero
- Eulàlia Grau (ORCID: https://orcid.org/0000-0002-2442-9165)
- Elena Vendrame (ORCID: https://orcid.org/0000-0002-5595-1773)
- Jordi Navarro (ORCID: https://orcid.org/0000-0002-7187-0367)
- Bibiana Planas (ORCID: https://orcid.org/0000-0002-1490-7127)
- Cristina Díez (ORCID: https://orcid.org/0000-0002-3508-9979)
- Peré Domingo (ORCID: https://orcid.org/0000-0003-1138-5770)
- Samuel Martín‐Vílchez (ORCID: https://orcid.org/0000-0003-0557-7653)
- Javier Queiruga
- Anuska Llano (ORCID: https://orcid.org/0000-0002-0133-9888)
- Margarita Ramírez (ORCID: https://orcid.org/0000-0002-4666-0114)
- Romas Geleziunas (ORCID: https://orcid.org/0000-0002-9290-8811)
- Susana Benet (ORCID: https://orcid.org/0000-0002-2219-8826)
- Meritxell Genescà (ORCID: https://orcid.org/0000-0001-6413-3812)
- Camila Piatti
- Christian Brander (ORCID: https://orcid.org/0000-0002-0548-5778)
- Lucio García‐Fraile (ORCID: https://orcid.org/0000-0002-2512-6107)
- Roger Paredes (ORCID: https://orcid.org/0000-0002-6553-691X)
- Santiago Moreno (ORCID: https://orcid.org/0000-0002-2843-1094)
- José M Miró (ORCID: https://orcid.org/0000-0002-7385-2664)
- Juan González (ORCID: https://orcid.org/0000-0003-3109-5586)
- Anna Ferrer (ORCID: https://orcid.org/0000-0001-5538-9349)
- Juan Carlos López Bernaldo de Quirós
- Rafael Micán
- Daina Lim (ORCID: https://orcid.org/0009-0007-5184-6339)
- Aroa Nieto
- Cristina Martínez
- Susan Guo
- Michelle Frankot
- Alvaro Aranguen
- Tamara De la Torre-Muñoz
Institutions
- Universitat de Vic - Universitat Central de Catalunya (ES)
- Universitat Autònoma de Barcelona (ES)
- University of Pittsburgh (US)
- Hospital Universitario La Paz (ES)
- Instituto de Salud Carlos III (ES)
- Hospital de Sant Pau (ES)
- Bellvitge University Hospital (ES)
- Hospital General Universitario Gregorio Marañón (ES)
- IrsiCaixa (ES)
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Vall d'Hebron Institut de Recerca (ES)
- Centro de Investigación Biomédica en Red (ES)
- Instituto Ramón y Cajal de Investigación Sanitaria (ES)
- Vall d'Hebron Hospital Universitari (ES)
- Hospital Universitario de La Princesa (ES)
- Gilead Sciences (United States) (US)
- Hospital Universitari Germans Trias i Pujol (ES)
- Fundació Clínic per a la Recerca Biomèdica (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Instituto de Investigación de Enfermedades Raras (ES)
- Hospital Universitario Ramón y Cajal (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-04
- DOI
- https://doi.org/10.1038/s41467-025-57284-w
- Citations
- 21
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 21.76