ALVAC-HIV / National Institute of Allergy and Infectious Diseases, Sanofi - LARVOL DELTA

Early neutrophil recruitment after heterologous late boost with and without new adjuvant in RV546 potentially contributes to vaccine-specific antibody responses (HIVR4P 2024) - "Here we assess fresh neutrophil responses upon heterologous booster vaccination with and without the Army Liposomal Formulation with QS21 (ALFQ) adjuvant. RV546 enrolled participants receiving RV144 ALVAC-HIV/AIDSVAX B/E prime/boost vaccine regimen followed by late boosts (RV306) who then received an additional heterologous boost 6-8 years later with gp120-CD4 IHV01 and gp120 A244 with or without ALFQ adjuvant... Overall, neutrophils are recruited early after vaccination potentially contributing to a transient inflammatory environment and providing B cell help, both required for induction of vaccine-specific antibody responses, further adjuvanted by ALFQ. These results warrant additional interrogations into the role of neutrophils during initial vaccine responses."

Clinical • Human Immunodeficiency Virus • Infectious Disease • CD4 • CEACAM8 • IL21

The vaginal microbiome pre-vaccination associates with local and systemic HIV vaccine immune responses (HIVR4P 2024) - "Here we assess the relationship between the vaginal microbiome and vaccine-induced binding antibody (BAb) responses. Cervicovaginal mucus samples were collected from participants (n=95) receiving the RV144 ALVAC-HIV/AIDSVAX B/E prime/boost vaccine regimen at baseline and 2 weeks post-RV144 prime/boost regimen... These data suggest an association between the vaginal microbiome and vaccine-induced BAb responses, with a more inflammatory polymicrobial environment being associated with lower vaccine-specific BAb levels. These results warrant further interrogations into the potential mechanisms by which the vaginal microbiome may impact vaccine responses and could inform interventional strategies."

Human Immunodeficiency Virus • Infectious Disease

Sex-specific immune responses to ALVAC-HIV and bivalent subtype C gp120/MF59 in the HVTN 100 clinical trial in South Africa (HIVR4P 2024) - "We found selected differences in immune responses by sex assigned at birth for the HVTN 100 vaccine regimen; however, these varied by immune response type. Although this regimen proved inefficacious regardless of sex-assigned-at-birth, future HIV vaccine trials should investigate whether there are sex-specific differences in immunogenicity and efficacy."

Clinical • Cytomegalovirus Infection • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8 • GZMB • IFNG • IL2

Non-HIV Vaccine-Induced Immune Responses as Potential Baseline Immunogenicity Predictors of ALVAC-HIV and AIDSVAX B/E-Induced Immune Responses. (PubMed, Viruses) - "The fourth significant correlation [(rho = 0.361; 95% CI: 0.049, 0.609; p = 0.021; FDR = 0.137)] was between CD4+ T-cell responses to a hepatitis B surface antigen peptide pool, measured 2 weeks after the third HBV vaccination, and IgG-binding antibody responses to gp70BCaseAV1V2 (B V1V2 immune correlate), measured two weeks after the second ALVAC-HIV and AIDSVAX B/E boost. These moderate correlations imply that either vaccine, TT or HBV, could potentially provide a moderately useful immunogenicity predictor for the ALVAC-HIV and AIDSVAX B/E HIV vaccine regimen."

Clinical • Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Tetanus • CD4

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

Potential novel vaccine adjuvant to enhance ADCC-mediated NK cells in the HIV preventive vaccines (AIDS 2024) - "BACKGROUND: The RV144 trial, with ALVAC-HIV and alum-adjuvanted AIDSVAX B/E gp120, remains the only HIV vaccine providing partial protection... The findings suggest that I3C modulates NK cells to enhance ADCC, indicating its potential as an adjuvant in HIV vaccine platforms such as RV144, with the capacity to improve HIV vaccine efficacy."

Clinical • Human Immunodeficiency Virus • Infectious Disease • FCGR3A • ITGAM • KLRG1 • TNFA

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

Safety and immunogenicity of a subtype C ALVAC-HIV and bivalent subtype C gp120 vaccine regimen adjuvanted with MF59 or Alum in a phase 1/2a randomized clinical trial (AIDS 2024) - "Although MF59 was expected to enhance immune responses, alum induced similar binding antibody and cellular responses to MF59, suggesting that the choice between these adjuvants may not be critical for the ALVAC+gp120 regimen for these immune responses."

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

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

Innate immune cell activation after HIV-1 vaccine administration is associated with increased antibody production. (PubMed, Front Immunol) - "Inclusion of ALVAC-HIV in the boost did not further increase MAIT, iNKT, γδ T, and NK cell activation or increase the proportion of non-classical monocytes...Finally, we observed trending associations between MAIT cell activation and Env-specific IgG3 titers and between NK cell activation and TH023 pseudovirus neutralization titers. Our study identifies a potential role for innate cells, specifically NK, MAIT, and γδ T cells, in promoting antibody responses following HIV-1 vaccine administration."

Clinical • Immune cell • Journal • Human Immunodeficiency Virus • Infectious Disease • CD14 • CD69

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

Novel V1 deleted-envelope vaccine based on VLP protects against SHIV infection (IAS-HIV 2023) - "DV1 or WT gp160 combined with p55Gag DNA vaccine were given at week 0, 4, followed by two immunizations with ALVAC-HIV at week 8 and 12; one WT or DV1 HIV A244 gp120 protein boost in alum was given at week 12... Thus, for reasons that are unclear at present, we conclude that V1 affects protective responses against HIV and further studies will be needed to address the mechanism(s)."

Human Immunodeficiency Virus • Infectious Disease • CCR2 • CD14

Additional boosting to the RV144 vaccine regimen increased Fc-mediated effector functions magnitude but not durability. (PubMed, AIDS) - P2 | "Additional boosting of RV144 improved the magnitude but not the durability of some Fc mediated effector functions that were associated with vaccine efficacy, with trogocytosis being the most durable."

Clinical • Journal • Human Immunodeficiency Virus • Infectious Disease

Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response. (PubMed, PLoS Pathog) - P1, P1/2, P2, P3 | "The RV305 HIV-1 clinical trial evaluated the immunological impact of a follow-up boost of HIV-1-uninfected RV144 recipients after 6-8 years with RV144 immunogens (ALVAC-HIV alone, AIDSVAX B/E gp120 alone, or ALVAC-HIV + AIDSVAX B/E gp120)...Trial registration: RV305 clinical trial (ClinicalTrials.gov number, NCT01435135). ClinicalTrials.gov Identifier: NCT00223080, ClinicalTrials.gov Identifier: NCT01931358, ClinicalTrials.gov Identifier: NCT01923610, ClinicalTrials.gov Identifier: NCT01461447."

Journal • Viral vector • Human Immunodeficiency Virus • Infectious Disease

ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone. (PubMed, JCI Insight) - "Lastly, levels of the Fc-mediated effector functions antibody-dependent cellular cytotoxicity, NK cell activation, and trogocytosis were significantly increased in participants who received ALVAC-HIV compared with those receiving AIDSVAX B/E alone. Taken together, these results suggest that ALVAC-HIV plays an essential role in developing cellular and humoral immune responses to protein-boosted regimens relative to protein alone."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Study of Late Boost Strategies for HIV-uninfected Participants From Protocol RV 144 (clinicaltrials.gov) - P2; N=162; Active, not recruiting; Sponsor: U.S. Army Medical Research and Materiel Command; Trial primary completion date: Oct 2013 ->Dec 2015

Trial primary completion date