CD40.HIVRI.Env / ANRS - LARVOL DELTA

Clinical Trial to Evaluate the Safety and Immunogenicity of Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env (VRIPRO) in Adult Participants Who Previously Participated in HVTN 706 (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Clinical Trial to Evaluate the Safety and Immunogenicity of Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env (VRIPRO) in Adult Participants Who Previously Participated in the HVTN706/MOSAICO Study and Remain Without HIV (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Initiation date: May 2025 ➔ Dec 2025

Trial initiation date • Human Immunodeficiency Virus • Infectious Disease

Clinical Trial to Evaluate the Safety and Immunogenicity of Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env (VRIPRO) in Adult Participants Who Previously Participated in the HVTN706/MOSAICO Study and Remain Without HIV (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Initiation date: Feb 2025 ➔ May 2025

Trial initiation date • Human Immunodeficiency Virus • Infectious Disease

Unadjuvanted CD40.HIVRI.ENV Vaccine Late Boost Induces Durable Immune Responses: ANRS/VRI06 Trial (CROI 2025) - P1 | "The ANRS/VRI06 phase I trial (NCT04842682) enrolled 72 non HIV-infected volunteers to receive either 0·3, 1·0, or 3·0 mg of CD40.HIVRI.Env (TLR3-Hiltonol® adjuvanted) alone or co-administered with DNA-HIV-PT123 at weeks (W) 0, 4 and 24, randomized 5:1 active vs. placebo. A single late boost of CD40.HIVRI.Env, even unadjuvanted, was sufficient to maintain humoral and cellular long-term responses. These results reveal the potency of CD40-DC targeting vaccines to induce durable responses."

Clinical • Infectious Disease • CD40 • IFNG • IL2 • TLR3

Dose Escalation Trial of CD40.HIVRI.Env Vaccine Combined or Not With a DNA-HIV-PT123 HIV-1 Vaccine in Healthy Volunteers (clinicaltrials.gov) - P1 | N=72 | Completed | Sponsor: ANRS, Emerging Infectious Diseases | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

Safety and immunogenicity of CD40.HIVRI.Env, a dendritic cell-based HIV vaccine, in healthy HIV-uninfected adults: a first-in-human randomized, placebo-controlled, dose-escalation study (ANRS VRI06). (PubMed, EClinicalMedicine) - P1 | "Volunteers were randomized (5:1 active versus placebo) in groups receiving either 0.3, 1.0, or 3.0 mg CD40.HIVRI.Env (Hiltonol® adjuvanted) alone or co-administered with DNA-HIV-PT123 at weeks (W) 0, 4, and 24. CD40 targeting Env-based vaccines may be instrumental for inducing protective vaccine responses in prime-boost strategies. ANRS Emerging infectious diseases (ANRS MIE); Vaccine Research Institute (VRI)."

Journal • P1 data • Human Immunodeficiency Virus • Infectious Disease • CD40 • IFNG • IL2

Clinical Trial to Evaluate the Safety and Immunogenicity of Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env (VRIPRO) in Adult Participants Who Previously Participated in the HVTN706/MOSAICO Study and Remain Without HIV (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

New P1 trial • Human Immunodeficiency Virus • Infectious Disease • CD40

Boosting HIV-1 immunity: unveiling the impact of antigen delivery systems in vaccination strategies (HIVR4P 2024) - P1 | "We investigated vaccine combinations containing the same antigens but using different platforms to enhance DNA-primed immune reactions: i) DNA-PT123 encoding HIV-1 Env(ZM96)-/Gag/Pol; ii) MVA-HIV-B encoding Gag/Pol/Nef; iii) Antigen-presenting cell (APC) targeting vaccines: anti-CD40 mAb fused with a string of 5 HIV-1 peptides (Gag/Pol/Nef: CD40.HIV5pep) or HIV-1 Env(ZM96) (CD40.HIVRI.Env) (tested in a recent phase I clinical trial NCT04842682). Female hCD40-transgenic mice were given prime injections of DNA-PT123 (50 mcg, i.m.) boosted either with i) MVA-HIV-B alone (107 PFU, i.m; Gr1); ii) MVA-HIV-B plus CD40.HIVRI.Env (10 mcg, i.p; Gr2); iii) CD40.HIV5pep (10 mcg, i.p.) plus CD40.HIVRI.Env (10 mcg, i.p)(Gr3) at week-3 (w3) and-5... Our results revealed a key role of vaccine platforms in eliciting specific immune responses regardless of antigens and confirmed the potency of a heterologous DNA prime/boost vaccination approach. We demonstrated the tuning effect of..."

Human Immunodeficiency Virus • Infectious Disease

Dose Escalation Trial of CD40.HIVRI.Env Vaccine Combined or Not With a DNA-HIV-PT123 HIV-1 Vaccine in Healthy Volunteers (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: ANRS, Emerging Infectious Diseases | Recruiting ➔ Active, not recruiting | Trial primary completion date: Sep 2023 ➔ Nov 2024

Enrollment closed • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

CD40.HIVRI.Env VACCINE INDUCES STRONG AND DURABLE IMMUNE RESPONSES: ANRS VRI06 TRIAL (CROI 2023) - P1 | "We hypothesized that administration of different doses of CD40.HIVRI.Env vaccine adjuvanted with TLR3 Poly-ICLC Hiltonol® will be safe and immunogenic. CD40.HIVRI.Env was safe and induced early, potent and durable anti-Env and V1/V2 IgG and polyfunctional CD4 T-cell responses, markers associated with reduced risk of infection in RV144. Co-administration of CD40.HIVRI.Env with DNA HIV-PT-123 is currently assessed in additional groups of the trial. CD40-DC targeting Env-based vaccines may be instrumental in strategies combining vaccine regimens, particularly Env protein-based vaccines, to induce durable responses."

IO biomarker • Late-breaking abstract • Human Immunodeficiency Virus • Immune Modulation • Infectious Disease • CD40 • IFNG • IL2 • TLR3 • TNFA

Dose Escalation Trial of CD40.HIVRI.Env Vaccine Combined or Not With a DNA-HIV-PT123 HIV-1 Vaccine in Healthy Volunteers (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: ANRS, Emerging Infectious Diseases | Trial completion date: Dec 2023 ➔ Sep 2024 | Trial primary completion date: Dec 2022 ➔ Sep 2023

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Immune Modulation • Infectious Disease