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

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

Published in

Scientific reports. Volume 16. Issue 1. May 29, 2026. Epub May 29, 2026.

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).

PMID:
42215520
Bibliographic data and abstract were imported from PubMed on 07 Sep 2026.

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