CD40.HIVEnv, an antibody mediated vaccine, induces long-term and recall immunogenicity in non-HIV-1 infected volunteers

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).

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Journal
Scientific Reports
Published
2026-05-29
DOI
https://doi.org/10.1038/s41598-026-52363-4
Primary Topic
HIV Research and Treatment
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article
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article

CD40.HIVEnv, an antibody mediated vaccine, induces long-term and recall immunogenicity in non-HIV-1 infected volunteers

Linda Wittkop, Géraldine Laumond, Aurélie Wiedemann, Hakim Hocini et al.
Scientific Reports
HIV Research and Treatment
article

CD40.HIVEnv, an antibody mediated vaccine, induces long-term and recall immunogenicity in non-HIV-1 infected volunteers

Linda Wittkop, Géraldine Laumond, Aurélie Wiedemann, Hakim Hocini, Vanessa Christinet, Béatrice Parfait, Mélany Durand, Kahina Cheref, Harouna Diombera, Léa Levoyer, Corinne Krief, Frédéric Batteux, Stéphane Paul, Philippe Kiehl, Marta Zatta, Hanane Mehawej, Camille Gilbert, Liem Binh Luong, Francesco Tommasini, Aline Voidey, Sylvie Schmidt, Véronique Rieux, Boris P. Hejblum, Emile Foucat, Raida Ben Rayana, Christiane Moog, Thomas Decoville, Muriel Verlinde‐Carvalho, Laura Molinari, Mireille Centlivre, Laure Surgers, Motolete Alaba Tanah, Liyun Li, Laurent Hanot, Corinne Guérin, Fabio Candotti, Lucile Hardel, Noémie Mercier, Tugba Agyar, Alpha Diallo, Craig Fenwick, Sylvain Cardinaud, Odile Launay, Magali Bouvier, ANRS VRI06 Study Group, Gerard Zurawski, Tapia Gonzalo, Jean-Daniel Lelièvre, Georgia D. Tomaras, Laurène Borie, Emma Jousseaume, Yves Levy, Sandra Zurawski, Sophie Grabar, Rodolphe Thiebaut, Mathilde Desvallées, Jean-Paul Viard, Pascal Grange, Christine Lacabaratz, Mathilde Favreau, Hélène Pollard, Marie Lachatre, Isabelle Sommer, Song Ding, Laura Richert, Giuseppe Pantaleo
article en

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).

Scientific Reports
Centre National de la Recherche Scientifique (FR), Institut national de recherche en sciences et technologies du numérique (FR), Université de Bordeaux (FR), Inserm (FR), Duke University (US), Université Paris-Est Créteil (FR), Université Paris Cité (FR), Paris-Est Sup (FR), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire Henri-Mondor (FR), Sorbonne Université (FR), Hôpital Cochin (FR), Assistance Publique – Hôpitaux de Paris (FR), Hôpital Saint-Antoine (FR), Bordeaux Population Health (FR), Baylor Medical Center at Garland (US), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (FR), Institut de Recherche Vaccinale (FR), Centre d'Immunologie et des Maladies Infectieuses (FR), Institut Pierre Louis d‘Épidémiologie et de Santé Publique (FR), Institut Cochin (FR), Eurovacc Foundation (CH), Hôpital Albert-Chenevier (FR), Centre Hospitalier Universitaire de Saint-Étienne (FR), Institut Mondor de Recherche Biomédicale (FR), Panjab University (IN), Université de Strasbourg (FR), University of Lausanne (CH)
Agence Nationale de la Recherche
Good health and well-being
Openalex Percentile: Top 7%
HIV Research and Treatment
DOIOpen Access PDFOpenAlex
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