Ad26.Mos4.HIV / J&J - LARVOL DELTA

Navigating the Complexities of HIV Vaccine Development: Lessons from the Mosaico Trial and Next-Generation Development Strategies. (PubMed, Vaccines (Basel)) - "This study aims to critically examine the obstacles encountered in HIV vaccine development, with a focus on the Mosaico trial, which tested the Ad26.Mos4.HIV vaccine among 3,900 participants across multiple countries...The integration of artificial intelligence (AI) into vaccine design offers new opportunities to optimize immunogenic targets, which could significantly improve the potential for durable and broad immune protection. The development of a successful HIV vaccine by 2030 is achievable but relies on leverage on advanced technologies including artificial intelligence, innovation and insights from past trial data."

Journal • Human Immunodeficiency Virus • Infectious Disease

RV591: Evaluation of Safety and Immunogenicity of Ad26.Mos4.HIV and CH505 TF chTrimer Combination in Healthy Adults (clinicaltrials.gov) - P1 | N=78 | Recruiting | Sponsor: U.S. Army Medical Research and Development Command | Not yet recruiting ➔ Recruiting | N=50 ➔ 78 | Trial completion date: Sep 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

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

Incidence and Predictors of STIs and Effect on Immune Activation in the HVTN 705/HPX2008 Trial (CROI 2025) - "Methods We conducted a secondary analysis of HVTN 705/HPX2008, a phase 2b placebo-controlled efficacy trial of Ad26.Mos4.HIV and aluminum phosphate-adjuvanted clade C gp140 in preventing HIV-1 infection in cisgender women aged 18 to 35 in Malawi, Mozambique, South Africa, Zambia and Zimbabwe...Risk of incident STIs was higher among women with recent anal sex or prior STI. Generally, Chlamydia infection does not appear to result in differences in baseline immune activation and should not alter immune responses to vaccination."

Human Immunodeficiency Virus • Infectious Disease • CD123 • IL3RA

Safety, Immunogenicity, Efficacy of Ad26.Mos4.HIV, MVA-BN-HIV and PGT121, PGDM1400, and VRC07-523LS in HIV-1-Infected Adults (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: Boris Juelg, MD PhD | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease • Primary Immunodeficiency • CD4

HLA-B*07:02 associated with higher vaccine efficacy in the phase 2b imbokodo trial among young cisgender women with increased likelihood of HIV acquisition in Southern Africa (HIVR4P 2024) - P2b | "BACKGROUND: The Phase 2b Imbokodo study (HVTN 705/HPX2008; NCT03060629) evaluated an investigational HIV-1 vaccine regimen, consisting of a vector-based vaccine (Ad26.Mos4.HIV) combined with clade C gp140 protein, among young cisgender women behaviorally vulnerable to HIV in Southern Africa... We demonstrate a VE of 86% among HLA-B*07:02 positive participants in the Imbokodo trial. HLA-B*07:02 was reported in association with a broad and potent response targeting Gag epitopes in the literature. Further epitope mapping will elucidate potential mechanisms of vaccine protection."

Clinical • P2b data • Human Immunodeficiency Virus • Infectious Disease • HLA-B • HLA-DPA1 • HLA-DRB5

Three year durability and boosting of T cell responses in the ASCENT study utilizing two HIV-1 vaccine regimens comprising of Ad26.Mos4.HIV and either clade C gp140 or bivalent gp140 (HIVR4P 2024) - P1/2 | "In this 3-year post-vaccination follow-up of ASCENT with additional late boost, we observed durable cellular immune responses in the participants receiving the Ad26.Mos.HIV plus gp140 bivalent vaccine regimen. Responses after the final boost at Wk192 were even higher than after the 4th primary dose. This demonstrates robust durable cellular responses induced by the Ad26/protein platform, highlighting a compelling feature where prolonged cellular responses would be desirable."

Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8 • IL2

Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study. (PubMed, EBioMedicine) - "The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen."

Journal • Allergy • Human Immunodeficiency Virus • Immunology • Infectious Disease • CD4 • CD8

Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial. (PubMed, Lancet Infect Dis) - P2b | "The heterologous Ad26.Mos4.HIV and clade C gp140 vaccine regimen was safe and well tolerated but did not show efficacy in preventing HIV-1 acquisition in a population of young women in southern Africa at risk of HIV-1."

Journal • P2b data • Allergy • Human Immunodeficiency Virus • Immunology • Infectious Disease

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

Immunogenicity of 2 therapeutic mosaic HIV-1 vaccine strategies in individuals with HIV-1 on antiretroviral therapy. (PubMed, NPJ Vaccines) - "In this double-blind, placebo-controlled phase 1 trial (IPCAVD013/HTX1002) 25 ART-suppressed PLWH were randomized to receive Ad26.Mos4.HIV/MVA-Mosaic (Ad26/MVA) (n = 10) or Ad26.Mos4.HIV/Ad26.Mos4.HIV plus adjuvanted gp140 protein (Ad26/Ad26+gp140) (n = 9) or placebo (n = 6)...Both vaccine regimens were immunogenic, while the addition of the protein boost resulted in additional T cell and augmented binding and neutralizing antibody titers. These data suggest that the Ad26/Ad26+gp140 regimen should be tested further."

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

RV582: Safety and Efficacy of Neutralizing Antibodies and Vaccination for Induction of HIV Remission (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine | N=35 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Human Immunodeficiency Virus • Infectious Disease • CD4

IPCAVD-012: A Safety, Tolerability and Immunogenicity Study of 2 Different Regimens of Tetravalent Ad26.Mos4.HIV Prime Followed by Boost With Tetravalent Ad26.Mos4.HIV Along With Either Clade C gp140 Plus Adjuvant OR With a Combination of Mosaic and Clade C gp140 Plus Adjuvant in Healthy HIV Uninfected Adults (clinicaltrials.gov) - P1/2 | N=155 | Completed | Sponsor: Janssen Vaccines & Prevention B.V. | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

RV591: Evaluation of Safety and Immunogenicity of Ad26.Mos4.HIV and CH505 TF chTrimer Combination in Healthy Adults (clinicaltrials.gov) - P1 | N=50 | Not yet recruiting | Sponsor: U.S. Army Medical Research and Development Command

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

MOSAICO: A Study of Heterologous Vaccine Regimen of Adenovirus Serotype 26 Mosaic4 Human Immunodeficiency Virus(Ad26.Mos4.HIV), Adjuvanted Clade C gp140 and Mosaic gp140 to Prevent HIV-1 Infection Among Cis-gender Men and Transgender Individuals Who Have Sex With Cis-gender Men and/or Transgender Individuals (clinicaltrials.gov) - P3 | N=3900 | Completed | Sponsor: Janssen Vaccines & Prevention B.V. | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

Safety, Immunogenicity, Efficacy of Ad26.Mos4.HIV, MVA-BN-HIV and PGT121, PGDM1400, and VRC07-523LS in HIV-1-Infected Adults (clinicaltrials.gov) - P1/2 | N=36 | Recruiting | Sponsor: Boris Juelg, MD PhD | Trial completion date: Mar 2025 ➔ Apr 2026 | Trial primary completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • Primary Immunodeficiency • CD4

MOSAICO: A Study of Heterologous Vaccine Regimen of Adenovirus Serotype 26 Mosaic4 Human Immunodeficiency Virus(Ad26.Mos4.HIV), Adjuvanted Clade C gp140 and Mosaic gp140 to Prevent HIV-1 Infection Among Cis-gender Men and Transgender Individuals Who Have Sex With Cis-gender Men and/or Transgender Individuals (clinicaltrials.gov) - P3 | N=3900 | Active, not recruiting | Sponsor: Janssen Vaccines & Prevention B.V. | Trial completion date: Mar 2024 ➔ Aug 2023

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

Safety, Immunogenicity, Efficacy of Ad26.Mos4.HIV, MVA-BN-HIV and PGT121, PGDM1400, and VRC07-523LS in HIV-1-Infected Adults (clinicaltrials.gov) - P1/2 | N=36 | Recruiting | Sponsor: Boris Juelg, MD PhD | Trial completion date: Mar 2024 ➔ Mar 2025 | Trial primary completion date: Mar 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • Primary Immunodeficiency • CD4

A Study to Assess the Efficacy of a Heterologous Prime/Boost Vaccine Regimen of Ad26.Mos4.HIV and Aluminum Phosphate-Adjuvanted Clade C gp140 in Preventing Human Immunodeficiency Virus (HIV) -1 Infection in Women in Sub-Saharan Africa (clinicaltrials.gov) - P2b | N=2636 | Terminated | Sponsor: Janssen Vaccines & Prevention B.V. | Completed ➔ Terminated; Study was terminated by the sponsor after the last participant completed the Month 24 visit as the pre-specified criteria to continue the study were not met.

Trial termination • Human Immunodeficiency Virus • Infectious Disease • IFNG

MOSAICO: A Study of Heterologous Vaccine Regimen of Adenovirus Serotype 26 Mosaic4 Human Immunodeficiency Virus(Ad26.Mos4.HIV), Adjuvanted Clade C gp140 and Mosaic gp140 to Prevent HIV-1 Infection Among Cis-gender Men and Transgender Individuals Who Have Sex With Cis-gender Men and/or Transgender Individuals (clinicaltrials.gov) - P3 | N=3900 | Active, not recruiting | Sponsor: Janssen Vaccines & Prevention B.V. | Trial primary completion date: Mar 2024 ➔ Aug 2023

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

RV582: Safety and Efficacy of Neutralizing Antibodies and Vaccination for Induction of HIV Remission (clinicaltrials.gov) - P1 | N=35 | Not yet recruiting | Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

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

Immune correlates analysis of the Imbokodo HIV-1 vaccine efficacy trial (AIDS 2022) - P2b | "BACKGROUND: In the phase 2b Imbokodo clinical trial (HVTN 705/HPX2008; NCT03060629), the investigational HIV vaccine regimen consisting of a vector-based vaccine (Ad26.Mos4.HIV) in combination with clade C gp140 protein was evaluated... Multiple statistical analyses revealed a trend of high IgG3 V1V2 BAMA breadth scores associated with lower infection risk and partial vaccine protection."

Clinical • Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease

Safety, Tolerability and Immunogenicity Study of Different Vaccine Regimens of Trivalent Ad26.Mos.HIV or Tetravalent Ad26.Mos4.HIV Along With Clade C Glycoprotein (gp)140 in Healthy Human Immunodeficiency Virus (HIV)-Uninfected Adults (clinicaltrials.gov) - P1/2 | N=201 | Completed | Sponsor: Janssen Vaccines & Prevention B.V. | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Immunology • Infectious Disease • IFNG • IL2 • IL4 • TNFA

Safety, Immunogenicity, Efficacy of Ad26.Mos4.HIV, MVA-BN-HIV and PGT121, PGDM1400, and VRC07-523LS in HIV-1-Infected Adults (clinicaltrials.gov) - P1/2 | N=36 | Recruiting | Sponsor: Boris Juelg, MD PhD | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Immunology • Infectious Disease • Primary Immunodeficiency • CD4

A Study to Assess the Efficacy of a Heterologous Prime/Boost Vaccine Regimen of Ad26.Mos4.HIV and Aluminum Phosphate-Adjuvanted Clade C gp140 in Preventing Human Immunodeficiency Virus (HIV) -1 Infection in Women in Sub-Saharan Africa (clinicaltrials.gov) - P2b | N=2637 | Completed | Sponsor: Janssen Vaccines & Prevention B.V. | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Immunology • Infectious Disease

Safety, Tolerability and Immunogenicity Study of Different Vaccine Regimens of Trivalent Ad26.Mos.HIV or Tetravalent Ad26.Mos4.HIV Along With Clade C Glycoprotein (gp)140 in Healthy Human Immunodeficiency Virus (HIV)-Uninfected Adults (clinicaltrials.gov) - P1/2 | N=201 | Active, not recruiting | Sponsor: Janssen Vaccines & Prevention B.V. | Trial completion date: Apr 2023 ➔ May 2022

Trial completion date • Human Immunodeficiency Virus • Immunology • Infectious Disease • IFNG • IL2 • IL4 • TNFA