DNA-HIV-PT123 vaccine / EuroVacc, National Institute of Allergy and Infectious Diseases - LARVOL DELTA

A Prophylactic HIV Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Clade C DREP Alone and in Combination With a Clade C ENV Protein in Healthy HIV-uninfected Adults (clinicaltrials.gov) - P1 | N=68 | Completed | Sponsor: ANRS, Emerging Infectious Diseases | Active, not recruiting ➔ Completed

Trial completion • 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

PrEPVacc: A Combination Efficacy Study in Africa of Two DNA-MVA-Env Protein or DNA-Env Protein HIV-1 Vaccine Regimens With PrEP (clinicaltrials.gov) - P2 | N=1512 | Completed | Sponsor: MRC/UVRI and LSHTM Uganda Research Unit | Enrolling by invitation ➔ Completed | Phase classification: P2b ➔ P2

Phase classification • Trial completion • 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 | 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

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

Comparative analysis of antibody responses to CN54gp140 and AIDSVAX B/E in the PrEPVacc trial (AIDS 2024) - "Participants were randomized to receive either (DNA HIV PT123 + AIDSVAX B/E) four times or (DNA HIV PT123 + CN54/MPLA) twice followed by (MVA-CMDR/CN54gp140/MPLA) twice or placebo over a 48-week vaccination period... This interim pooled analysis of a subset that completed 3 vaccinations suggests higher geometric mean titers of binding antibodies to CN54gp140 compared to AIDSVAX B/E at week 26. Further unblinded analysis of the full dataset will be presented at the meeting."

Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease

Safety and Immunogenicity of a DNA Vaccine With Subtype C gp120 Protein Adjuvanted With MF59 or AS01B: A Phase 1/2a HIV-1 Vaccine Trial. (PubMed, J Acquir Immune Defic Syndr) - P1/2 | "The vaccine regimens were generally well tolerated. Co-administration of DNA with AS01B-adjuvanted bivalent Env gp120 elicited the strongest humoral responses; AS01B-adjuvanted regimens elicited stronger CD4+ T-cell responses, justifying further evaluation.ClinicalTrials.gov registration: NCT02915016, registered 26 September 2016."

Clinical • Journal • P1/2 data • Human Immunodeficiency Virus • Infectious Disease • CD4

SWIFT clustering analysis of intracellular cytokine staining flow cytometry data of the HVTN 105 vaccine trial reveals high frequencies of HIV-specific CD4+ T cell responses and associations with humoral responses. (PubMed, Front Immunol) - "The HVTN 105 vaccine clinical trial tested four combinations of two immunogens - the DNA vaccine DNA-HIV-PT123, and the protein vaccine AIDSVAX B/E...In the complex HVTN105 dataset, alternative analysis methods increased sensitivity of the detection of antigen-specific T cells; increased the number of identified vaccine responders; identified a small IL-21-producing T cell population; and demonstrated significant correlations between specific T cell populations and serum antibody responses. Multiple analysis strategies may be valuable for extracting the most information from large, complex studies."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4 • IFNG • IL2 • IL21

A Prophylactic HIV Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Clade C DREP Alone and in Combination With a Clade C ENV Protein in Healthy HIV-uninfected Adults (clinicaltrials.gov) - P1 | N=68 | Active, not recruiting | Sponsor: ANRS, Emerging Infectious Diseases | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

A Prophylactic HIV Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Clade C DREP Alone and in Combination With a Clade C ENV Protein in Healthy HIV-uninfected Adults (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: ANRS, Emerging Infectious Diseases | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2023 ➔ Sep 2024 | Trial primary completion date: Jun 2022 ➔ Sep 2024

Combination therapy • Enrollment open • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

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

PrEPVacc: A Combination Efficacy Study in Africa of Two DNA-MVA-Env Protein or DNA-Env Protein HIV-1 Vaccine Regimens With PrEP (clinicaltrials.gov) - P2b | N=1668 | Enrolling by invitation | Sponsor: MRC/UVRI and LSHTM Uganda Research Unit | Not yet recruiting ➔ Enrolling by invitation | Trial completion date: Mar 2023 ➔ Dec 2024 | Trial primary completion date: Mar 2023 ➔ Dec 2024

Enrollment open • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Participants' characteristics and motivations to screen for HIV vaccine and monoclonal antibody trials in KwaZulu-Natal, South Africa. (PubMed, Trials) - P1, P1/2, P2b | "The current recruitment approach of these trials attracts heterosexual participants who seek to reduce HIV risk and support their community. Hence, the data suggest the need for and potential acceptance of continued ongoing HIV prevention efforts. Current trials attract participants with lower educational levels, which may be driven by the site locations, current community mobilisation strategies and research site opening hours. The sites could consider more flexible working hours to accommodate working participants and find ways to connect participants to educational support and opportunities to upgrade education levels for the current clientele."

Journal • Human Immunodeficiency Virus • Infectious Disease

Evaluating the Safety and Immune Response to Different Combinations of the DNA-HIV-PT123 and AIDSVAX® B/E Vaccines in Healthy, HIV-Uninfected Adults (clinicaltrials.gov) - P1b; N=104; Completed; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Phase classification: P1 ➔ P1b

Clinical • Phase classification • Human Immunodeficiency Virus • Infectious Disease • CD4 • PCR

Evaluating the Safety and Immune Response to Five Different Combinations of HIV Vaccines in Healthy, HIV-Uninfected Adults (clinicaltrials.gov) - P1b; N=0; Withdrawn; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Phase classification: P1 ➔ P1b

Clinical • Phase classification • Human Immunodeficiency Virus • Infectious Disease • CD4 • PCR

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; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Human Immunodeficiency Virus • Immune Modulation • Infectious Disease • PCR

A Prophylactic HIV Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Clade C DREP Alone and in Combination With a Clade C ENV Protein in Healthy HIV-uninfected Adults (clinicaltrials.gov) - P1; N=70; Not yet recruiting; Sponsor: ANRS, Emerging Infectious Diseases

New P1 trial • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

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; Not yet recruiting; Sponsor: ANRS, Emerging Infectious Diseases

New P1 trial • Human Immunodeficiency Virus • Immune Modulation • Infectious Disease • PCR

Evaluating the Safety and Immunogenicity of HIV Clade C DNA Vaccine and MF59- or AS01B-Adjuvanted Clade C Env Protein Vaccines in Various Combinations in Healthy, HIV-Uninfected Adults (clinicaltrials.gov) - P1/2; N=334; Completed; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Active, not recruiting ➔ Completed

Clinical • Trial completion