HIV vaccine vCP2438 / Sanofi, GSK - LARVOL DELTA

Retrospective analysis of sex-disaggregated immune responses to ALVAC-HIV and bivalent subtype C gp120/MF59 HIV vaccines. (PubMed, Front Immunol) - "We retrospectively analyzed data from HVTN 100, a clinical trial conducted in South Africa during which 143 adults AMAB and 109 AFAB aged 18-40 years without HIV received ALVAC-HIV vCP2438 plus bivalent subtype C gp120/MF59 or placebo at 0, 1, 3, 6, and 12 months. While vaccine recipients AFAB demonstrated higher ADCC responses, AMAB exhibited higher CD4+ T cell response rates. Future analyses should investigate whether vaccine factors such as platform, dosing and adjuvants contribute to sex-based differences in immunogenicity of experimental HIV vaccines."

Journal • Retrospective data • Human Immunodeficiency Virus • Infectious Disease • CD4 • GZMB • IFNG

Safety and immunogenicity after a 30-month boost of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120/MF59 vaccine boost (HVTN 100): A phase 1-2 randomized double-blind placebo-controlled trial. (PubMed, PLOS Glob Public Health) - P1/2 | "Because these responses waned after 6 months, additional strategies may be needed to maintain the durability of prime-boost vaccine regimens and to generate these or other immune responses that confer protection. Trial registration: South African National Clinical Trials Register (SANCTR number: DOH-27-0215-4796) and ClinicalTrials.gov (NCT02404311)."

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

ALVAC-prime and monomeric gp120 protein boost induces distinct HIV-1 specific antibody and cellular responses compared with adenovirus-prime and trimeric gp140 protein boost (AIDS 2024) - "It is important for future HIV-1 vaccine development to understand the similarities and differences in the immune responses elicited in these early phase vaccine trials. HVTN100 tested a clade B/C canarypox vector Gag/Env insert prime (ALVAC-HIV (vCP2438)) with ALVAC-HIV + clade C Env gp120/MF59 protein boosts. HVTN117/HPX2004 tested a tetravalent adenovirus serotype 26 vector with mosaic Gag/Pol/Env insert (Ad26.Mos4.HIV) followed by an alum-adjuvanted trimeric subtype C gp140 protein vaccination... Both regimens induced robust gp120- and gp140-specific IgG responses, while the HVTN117/HPX2004 regimen elicited more durable IgG V1V2 responses. In contrast, HVTN100 induced higher polyfunctional CD4+ Env T cells. Nevertheless, neither vaccine regimen demonstrated protection, suggesting that broader, and/or more robust immune responses likely including neutralization are needed for clinical protection against acquisition."

Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

Factors associated with reactogenicity to an investigational HIV vaccine regimen in HIV vaccine trials network 702. (PubMed, Vaccine) - "Vaccine receipt, female sex at birth, older age, and region may affect reactogenicity."

Journal • Human Immunodeficiency Virus • Infectious Disease • Musculoskeletal Pain • Pain

Safety and immunogenicity of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120 vaccine boost adjuvanted with MF59 or alum in healthy adults without HIV (HVTN 107): A phase 1/2a randomized trial. (PubMed, PLoS Med) - P1/2 | "Although MF59 was expected to enhance immune responses, alum induced similar responses to MF59, suggesting that the choice between these adjuvants may not be critical for the ALVAC+gp120 regimen."

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

Safety and Immunogenicity of Month 30 Boost of ALVAC+gp120/MF59 Preventive HIV Vaccines (CROI 2024) - "Background: HVTN 100, a phase 1-2 preventive HIV vaccine trial in South Africa, administered subtype C-containing ALVAC-HIV (vCP2438) at months 0 and 1, and ALVAC-HIV with bivalent subtype C gp120/MF59 at months 3, 6 and 12 in Part A. IgG binding antibody and T-cell responses were similar or greater at month 12.5 compared to month 6.5 then waned by month 18. Booster vaccination with gp120/MF59 given alone or with ALVAC after an 18-month interval was safe and induced binding, tier 1A neutralization and CD4+ T-cell responses similarly in both vaccine groups. Late boosting may increase breadth of responses and restore V1V2 binding antibody responses."

Clinical • Human Immunodeficiency Virus • Infectious Disease • CD4

HVTN702: Pivotal Phase 2b/3 ALVAC/Bivalent gp120/MF59 HIV Vaccine Prevention Safety and Efficacy Study in South Africa (clinicaltrials.gov) - P2/3 | N=5404 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Phase classification: P2b ➔ P2/3

Phase classification • Human Immunodeficiency Virus • Infectious Disease

Protein dose-sparing effect of AS01B adjuvant in a randomized preventive HIV vaccine trial of ALVAC-HIV (vCP2438) and adjuvanted bivalent subtype C gp120. (PubMed, J Infect Dis) - P1/2 | "The 40μg dose gp120/AS01B regimen elicited the highest CD4+ T-cell and binding antibody responses."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

HVTN702: Pivotal Phase 2b/3 ALVAC/Bivalent gp120/MF59 HIV Vaccine Prevention Safety and Efficacy Study in South Africa (clinicaltrials.gov) - P2b | N=5407 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

HVTN702: Pivotal Phase 2b/3 ALVAC/Bivalent gp120/MF59 HIV Vaccine Prevention Safety and Efficacy Study in South Africa (clinicaltrials.gov) - P2b; N=5407; Active, not recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Trial primary completion date: Feb 2021 ➔ Sep 2021

Clinical • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Evaluating the Safety and Immunogenicity of ALVAC-HIV and MF59®- or AS01B-adjuvanted Bivalent Subtype C gp120 in Healthy, HIV-uninfected Adult Participants (clinicaltrials.gov) - P1/2; N=160; Completed; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Trial completion date: Oct 2019 ➔ Jul 2020; Trial primary completion date: Oct 2019 ➔ Jul 2020

Clinical • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • IL2 • PCR

Kenya: What to Expect in 2021 (All Africa) - "There are three experimental HIV vaccines in the final stages whose results are expected to be released between 2021 and 2023. Scientists say they are optimistic the trial of HVTN 702, Imbokodo and Mosaico will yield good results. HVTN 702 is the oldest vaccine trial. Its development is based on another vaccine candidate, the RV144 whose clinical trial findings showed the vaccine lowered the rate of infection by about 30 per cent. Clinical results for HVTN 702 are expected in 2021. The results for Imbokodo, another vaccine candidate being tried in five southern Africa countries, are expected in 2021....Mosaico trial results are expected to be released in 2023."

Clinical data • P2b data • P3 data • Human Immunodeficiency Virus

HVTN702: Pivotal Phase 2b/3 ALVAC/Bivalent gp120/MF59 HIV Vaccine Prevention Safety and Efficacy Study in South Africa (clinicaltrials.gov) - P2b; N=5407; Active, not recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Trial completion date: Jul 2022 ➔ Aug 2021; Trial primary completion date: Jul 2022 ➔ Feb 2021

Clinical • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines. (PubMed, PLoS Med) - P1/2 | "In this study, a 12-month booster of subtype C pox-protein vaccines restored immune responses, and slowed response decay compared to the 6-month vaccination."

Clinical • Journal • P1 data • P2 data

HVTN107: Safety and Immunogenicity of Clade C ALVAC and gp120 HIV Vaccine (clinicaltrials.gov) - P1/2; N=132; Completed; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Active, not recruiting ➔ Completed; Trial completion date: Mar 2020 ➔ Dec 2019

Clinical • Trial completion • Trial completion date • PCR

Evaluating the Safety and Immunogenicity of ALVAC-HIV and MF59®- or AS01B-adjuvanted Bivalent Subtype C gp120 in Healthy, HIV-uninfected Adult Participants (clinicaltrials.gov) - P1/2; N=160; Completed; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Active, not recruiting ➔ Completed

Clinical • Trial completion