CD40.HIVEnv, an antibody mediated vaccine, induces long-term and recall immunogenicity in non-HIV-1 infected volunteers
Year: 2026
Type: article
Abstract: The ANRS VRI06 trial investigated CD40.HIVRI.Env, an Antibody Mediated Vaccine composed by a CD40 monoclonal antibody fused with gp140 Env, designed to target antigen to dendritic cells. Initial results in 72 HIV-uninfected volunteers showed that administration of 0.3-3.0 mg of CD40.HIVRI.Env, given alone or with DNA-HIV-PT123, was safe and immunogenic up to 48 weeks. After week 48 in the trial, 45 volunteers were randomized to receive a late boost (LB) of 0.3 mg CD40.HIVRI.Env, either with or without adjuvant, to assess continued safety and immunogenicity at 2 and 24 weeks post-LB. The median LB interval from VRI06 baseline was 80 and 79 weeks in unadjuvanted (n=23) and adjuvanted (n=22) groups, respectively. Env-specific IgG and functional CD4+ T-cells persisted at the time of the LB, a median of 55 weeks after the last injection at W24. The LB was well tolerated and markedly boosted immune responses. In particular: i) IgG response rates against gp140 and 9 gp120 antigens reached 100% (vaccine-matched) and 82-100% (heterologous) by 24 weeks post-LB; ii) response rates to gp70 V1V2 antigens increased substantially (e.g., from 0-5% to 5-35%) against autologous 96ZM651 and heterologous V1V2 antigens; iii) neutralizing titers against Tier 1 MW965.26 rose from 14-22% to 35-59%; iv) the frequency of polyfunctional Env-specific CD4+ T-cells increased and persisted 24 weeks post-LB. No marked differences were observed between adjuvanted and unadjuvanted LB groups. CD40.HIVRI.Env vaccination is safe and induced broad, potent and long-lasting anti-HIV immune responses recalled by a single late boost, even without adjuvant. Trial registration: Clinical Trials.gov NCT04842682 || https://www.clinicaltrials.gov/ (2021-04-13).
Source: Scientific Reports
Authors: Yves Levy, Christiane Moog, Aurélie Wiedemann, Odile Launay, Fabio Candotti, Lucile Hardel, Mélany Durand, Boris P. Hejblum, Véronique Rieux, Alpha Diallo, Christine Lacabaratz, Sylvain Cardinaud, Sandra Zurawski, Gerard Zurawski, Georgia D. Tomaras, Song Ding, Mireille Centlivre, Rodolphe Thiebaut, Giuseppe Pantaleo, Jean-Daniel Lelièvre, Laura Richert, ANRS VRI06 Study Group, Tugba Agyar, Motolete Alaba Tanah, Frédéric Batteux, Raida Ben Rayana, Laurène Borie, Magali Bouvier, Kahina Cheref, Vanessa Christinet, Thomas Decoville, Mathilde Desvallées, Harouna Diombera, Mathilde Favreau, Craig Fenwick, Emile Foucat, Camille Gilbert, Tapia Gonzalo, Sophie Grabar, Pascal Grange, Corinne Guerin, Laurent Hanot, Hakim Hocini, Emma Jousseaume, Philippe Kiehl, Corinne Krief, Marie Lachatre, Géraldine Laumond, Léa Levoyer, Li-Yun Li, Liem Binh Luong, Hanane Mehawej, Noémie Mercier, Laura Molinari, Stéphane Paul, Béatrice Parfait, Hélène Pollard, Sylvie Schmidt, Isabelle Sommer, Laure Surgers, Francesco Tommasini, Muriel Verlinde-Carvalho, Jean-Paul Viard, Aline Voidey, Linda Wittkop, Marta Zatta
Institutions: Inserm, Université Paris-Est Créteil, Assistance Publique – Hôpitaux de Paris, Institut de Recherche Vaccinale, Hôpitaux Universitaires Henri-Mondor, Hôpital Albert-Chenevier, Institut Mondor de Recherche Biomédicale, Université de Strasbourg, Centre Hospitalier Universitaire Henri-Mondor, Université Paris Cité, Hôpital Cochin, Centre d'Investigation Clinique de Vaccinologie Cochin-Pasteur, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Université de Bordeaux, Methods and Applied Research for Trial, Institut national de recherche en sciences et technologies du numérique, Bordeaux Population Health, SISTM: Statistics In System biology and Translational Medicine, Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Baylor Scott & White Research Institute, Duke University, Eurovacc Foundation, Centre Hospitalier Universitaire de Bordeaux, Sorbonne Université, Institut Pierre Louis d‘Épidémiologie et de Santé Publique, Centre Hospitalier Universitaire de Saint-Étienne, Hôpital Saint-Antoine, Centre National de la Recherche Scientifique, Hôtel-Dieu de Paris, Institut Cochin
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funder: Agence Nationale de la Recherche
Award: G2318518392
OpenAlex ID: W7162751027
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