VRC01 / National Institute of Allergy and Infectious Diseases, Acuitas Therap - LARVOL DELTA

Reasons for participation and experiences of women in an antibody-mediated HIV prevention clinical trial in Malawi. (PubMed, Pan Afr Med J) - "in the Antibody-Mediated Prevention (AMP) trials, a broadly neutralizing antibody called VRC01 was infused intravenously every two months to test its safety and HIV prevention efficacy...antibody-mediated prevention study participants enrolled and continued their participation because of perceived benefits such as access to quality health care, finances, and altruism. Provision of other health services to research participants promotes participation in the trials."

Journal • Human Immunodeficiency Virus • Infectious Disease

A kinetically constrained dynamic flux balance analysis model predicts diverse CHO-cell culture process modes and conditions. (PubMed, Metab Eng) - "Similarly, experimentally validated predictions of perfusion bioreactor performance showed that coupling historical fed-batch data with computational tools can be leveraged to predict continuous biomanufacturing performance. We thus demonstrate that the developed mathematical model can simulate culture performance across multiple operating modes and process conditions beyond those used for parameter regression for the CHO VRC01 cell line used in this study."

Journal • Preclinical

VRC01 exerted differential pressure on HIV-1 Env from subtypes B and C that continued in the first weeks post-diagnosis in the AMP trials. (PubMed, J Infect Dis) - "These findings show the impact of sieve acquisition (variants blocked among subtype B viruses) and post-acquisition (stronger impact of VRC01-mediated escape in subtype C) effects, highlighting a complex intersection between HIV-1 subtypes, escape pathways and antibody-mediated prevention. The differential pressure exerted by VRC01 on subtype B vs. C viruses emphasizes that escape pathways need to be considered when selecting bnAbs for clinical trials."

Journal • Human Immunodeficiency Virus • Infectious Disease

Computationally inspired glycoengineering to maximise mAb β4-galactosylation. (PubMed, Metab Eng) - "Here, we describe a dual genetic engineering strategy applied to two mAb-producing CHO cell lines, DP12 and VRC01, to simultaneously overcome the cellular machinery and metabolic bottlenecks that limit β4-galactosylation...C-/GT+ glycoengineering had no negative impact on mAb titre. Our results establish the C-/GT+ dual glycoengineering strategy as a robust approach for consistently achieving high mAb galactosylation across diverse cell culture conditions, with the additional benefit of reduced Man5 glycans."

Journal

HIV-1 antibody-mediated neutralization via a dual-glycan clamp. (PubMed, Cell Rep) - "The CD4bs antibodies were members of the VRC01-antibody class and neutralized nearly 70% of HIV-1 (208-strain panel). The glycan-reactive antibody had ∼30% breadth, and cryo-EM analysis revealed it to be a Fab-dimerized glycan (FDG)-reactive antibody with a distinct architecture wherein the Fab arms dimerized through a disulfide bond at the tips of the complementarity-determining loops that wedged between two glycans. Overall, we identified an FDG antibody that recognized through a "dual-glycan clamp" epitope and is the second FDG antibody to be isolated from an HIV-infected donor since antibody 2G12."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Evaluating an anti-idiotype derived germline-targeting immunogen designed to elicit VRC01-class precursors in human antibody transgenic mice. (PubMed, mSphere) - "Class-switched VRC01 precursors were detected in a minority of animals immunized with the modified iv4/iv9. Collectively, these results indicate that although the iv4/iv9 immunogen did not reproducibly elicit VRC01-class B cells, ATX-GK mice have utility to evaluate VRC01-class germline-targeting immunogens but are a stringent model due to a low frequency of VRC01-class B cells."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Preclinical and clinical trials for vaccine induction of CD4-binding site-neutralizing antibodies. (PubMed, Curr Opin HIV AIDS) - "With proof-of-concept for VRC01-class priming being achieved, the next challenge is to induce strong serum antibodies and memory B cells with breadth and potency. Progress toward a protective CD4bs-directed HIV-1 vaccine will require further optimization of adjuvants, delivery systems, and sequential immunogen design to balance precursor recruitment with structural constraint and to sustain affinity maturation across multidose regimens, ultimately driving rare lineages to durable bnAb responses in diverse populations."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease • CD4

Beyond one mutation at a time: λ-Dynamics from alanine scanning to mutational coupling in antibody bind (ACS-Fall 2026) - "Using neutral alanine-scanning mutations from three VRC01-class broadly neutralizing antibodies (VRC01, VRC03, VRC-PG04) bound to HIV-1 gp120, benchmarked against experimental surface plasmon resonance data, λ-dynamics achieves an RMSE below 1 kcal/mol with rank-order correlations comparable to FEP/REST, demonstrating accuracy approaching that of established methods at substantially lower computational cost...Extending beyond single mutations, we apply multisite λ-dynamics to charge-changing and combinatorial mutations from the AB-Bind database, where prediction accuracy depends on both the number of mutations per site and the total number of mutated sites — capturing mutational coupling that is uniquely accessible through multisite perturbation and out of reach for pairwise methods. Collectively, these results establish λ-dynamics as an accurate and scalable framework for antibody affinity prediction, approaching the accuracy of established methods such as FEP+ while..."

Human Immunodeficiency Virus • Infectious Disease

Body mass index as a predictor of HIV acquisition: post-hoc analysis of data from 3 HIV prevention trials (AIDS 2026) - " HVTN702 (ALVAC-HIV + gp120–MF59) included 3773 South African women followed for 24 months with 239 HIV acquisitions; HVTN703/HPTN081 (VRC01 monoclonal antibody) included 1,924 Southern African women followed for 19 months with 76 acquisitions; HVTN704/HPTN085 (VRC01) included 2,687 men and transgender women in the Americas/Switzerland with 98 acquisitions. Higher BMI was associated with lower HIV likelihood across 3 global HIV prevention trials. Further research is needed to understand the underlying mechanism(s) and the roles of other unobserved potential confounders."

Retrospective data • Human Immunodeficiency Virus • Infectious Disease • Obesity

Phase 1 trial of germline-targeting HIV-1 DNA vaccine elicits CD4 binding site specific broadly neutralizing precursor antibodies (AIDS 2026) - "BACKGROUND: HVTN 305 evaluated vaccination with a synthetic DNA self-assembling eOD-GT8 60-mer nanoparticle co-formulated with pIL-12 (INO-6172) to activate VRC01-like CD4 binding site (CD4bs)-specific germline B cell lineages... Synthetic DNA encoding eOD-GT8 elicited antigen-specific antibody and B-cell responses supporting use of INO-6172 as a CD4bs germline-targeting immunogen. Trimer 4571 did not improve CD4bs specific responses. Ongoing work will further elucidate the presence of CD4bs antibody maturation through B cell receptor sequencing."

P1 data • Human Immunodeficiency Virus • Infectious Disease • CD4

Extended hinge length of human IgG3-like antibody enhances early antiviral activity of VRC01 in SHIV-infected rhesus macaques. (PubMed, J Virol) - No abstract available

Journal • Human Immunodeficiency Virus

Vrc01-class Precursor Frequency in an African Population is Influenced by Ighv1-2 Allelic Composition and Not Malaria Exposure. (PubMed, Res Sq) - "Notably, a novel IGHV1-2 allele (IGHV1-2*06_S5416) demonstrated the ability to engage eOD-GT8, unlike the reference *06 allele. Overall, our results support the development of GT vaccines to induce VRC01-class bnAbs in this population and reiterate the need for participant genotyping in GT vaccine trials, particularly in African populations where genetic diversity is high yet understudied."

Journal • Human Immunodeficiency Virus • Infectious Disease • Malaria • CD4

Modeling quantifies in vivo neutralization, Fc-mediated killing, and resistance in human clinical trials of five anti-HIV broadly neutralizing antibodies. (PubMed, bioRxiv) - "We therefore performed a mathematical modeling meta-analysis which integrated four clinical trials and reproduced serial bnAb concentrations, viral loads, and bnAb sensitivities (IC50) in 43 viremic trial participants who received an infusion of VRC01, VRC01LS, VRC07-523LS, 3BNC117 or 10-1074. For each bnAb, our best model identified a scaling factor of 36-462 to pro j ect in vivo activity from in vitro IC50, quantified Fc-mediated infected cell killing in humans over time, and pro j ected the timing of bnAb-resistant strain emergence. Using this holistic profile, VRC07-523-LS was generally optimal."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease

Maturation of HIV-1 neutralizing antibodies in a germinal center conditional expression mouse model. (PubMed, PLoS Pathog) - "With this model, we established an immunization method to mature the VRC01 intermediate into heterologous neutralizing antibodies against viruses with a native glycan shield. Since high mutation load is common among bnAbs, the germinal center conditional expression system could provide a general tool for boost immunogen design to overcome roadblocks in the maturation pathway."

Journal • Preclinical • Tumor mutational burden • Human Immunodeficiency Virus • Infectious Disease • CD4 • TMB

Diverse germline-targeting HIV Env immunogens select for distinct mutations in the same knock-in mice B cell receptors. (PubMed, Nat Commun) - "VRC01-class HIV broadly neutralizing antibodies have been isolated from people living with HIV...Thus, while the same BCRs are initially activated, they follow different maturation pathways depending on the immunogen used. These findings have important implications not only for HIV vaccine design efforts but also for other immunogens aiming to direct specific BCR maturation pathways."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease

HIV tri-specific killer engagers directly enhance NK cell function and safely expand NK cells in vivo. (PubMed, Cell Rep Med) - "HIV TriKEs, one using the VRC01/07 antibody domains (VRC TriKE) and one using the CD4 ectodomain 1 (CD4 TriKE), promote NK cell function and killing of HIV target cells...The TriKE is safe and effective at expanding peripheral and lymphoid NK cells in vivo. These findings support TriKEs as a promising safe immunotherapy to recognize and kill HIV-infected cells, with potential for combination cure strategies."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease • B3GAT1 • CD4

VRC01 with antiretroviral initiation in infants is well tolerated, and higher concentrations associate with greater HIV-1 DNA declines. (PubMed, Sci Transl Med) - "These results highlight the safety of bNAbs for treatment of infants. Studies with more potent bNAbs are needed to assess effects on HIV-1 DNA during early treatment of infants living with HIV-1."

Clinical • Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Inhibition of HIV-1 cell-to-cell transmission in-vitro using engineered CAR NK/T cells. (IMMUNOLOGY 2026) - "Here, we studied the effects of immune-based strategies, including ADCC and CAR NK/T cells, on HIV-1 transmission between cells. We developed a highly sensitive assay for precise quantification of cell lysis using luciferase activity and built CAR NK/T based on the VRC01 and PGT121 bnAbs. These results provide proof of concept that targeting HIV-1 C-CT through ADCC and CAR NK/T cell therapies can overcome the limitations of bnAbs. This study offers the first evidence to test these approaches to effectively target HIV-1 C-CT, highlighting their potential in studying HIV-1 treatment strategies."

Preclinical • Human Immunodeficiency Virus • Infectious Disease

Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials. (PubMed, Nat Commun) - P2b | "In the treatment group there is evidence of recombinant viruses preferentially inheriting resistance-associated mutations. This study provides critical insights into viral genetic and antigenic diversity that needs to be targeted to achieve protection, and highlights the role of recombination in facilitating escape."

Journal • Human Immunodeficiency Virus • Infectious Disease

Dual role of glycosylation in resistance to CD4-binding site broadly neutralizing antibodies. (PubMed, J Virol) - "In this study, we demonstrate that glycan-mediated escape from VRC01-class bNAbs is highly context-dependent-shaped by Env, the bNAb, and the glycosylation patterns introduced by the producer cell. These findings emphasize the dual role of glycans in affecting antibody sensitivity (shielding the virus to increase antibody resistance or sometimes providing an epitope that increases antibody sensitivity) and underscore the importance of viral and host factors in shaping effective bNAb-based cure strategies across diverse HIV-1 strains."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Modeling HIV dynamics under broadly neutralizing antibodies: the potential role of cell-to-cell virus transmission. (PubMed, J Theor Biol) - "The model is calibrated using clinical data from six responding infected individuals receiving VRC01 infusion...These results highlight the potential role of cell-to-cell transmission in sustaining HIV infection despite bNAb pressure and the need to optimize dosing regimens to improve outcomes. These model-based predictions warrant further experimental and clinical investigation."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Differential contributions of human oligosaccharyltransferase complexes OST-A and OST-B to HIV-1 envelope glycoprotein glycosylation. (PubMed, J Virol) - "STT3A/3B knockout (KO) affected the neutralization sensitivity to broadly neutralizing antibodies (bNAbs) in a strain-specific manner, with STT3A-KO increasing susceptibility to VRC01 bNAb for the tested HIV-1 strains...Additionally, site-specific glycan analysis of recombinant Env proteins identified several STT3A-dependent sites and confirmed a dominant role of STT3B in C-terminal glycosylation. Our fundamental study contributes novel insights into host-cell-mediated glycosylation and informs the development of methods to regulate PNGS occupancy of Env-based immunogens."

Journal • Human Immunodeficiency Virus • Infectious Disease • STT3A

Immune correlates of HIV-1 rebound during broadly neutralizing antibody treatment in young children. (PubMed, J Clin Invest) - "We conducted a detailed analysis of proviral reservoir dynamics and antiviral immune responses in a unique group of young children from Botswana who started ART at birth and then stopped standard ART while receiving the bnAbs 10-1074 and VRC01-LS in a subsequent clinical trial. HIV-specific T cell responses were low in all study participants and unrelated to viral reservoir sizes or clinical outcomes following ART interruption. These results suggest that, in young children, specific NK cell subsets and KIR-HLA interactions might be linked to HIV-1 rebound kinetics after substitution of standard ART with bnAbs."

Clinical • Journal • Human Immunodeficiency Virus • Infectious Disease • HLA-B • KIR2DL1 • KLRC1

Divalent HIV-1 gp120 Immunogen Exhibits Selective Avidity for Broadly Neutralizing Antibody VRC01 Precursors. (PubMed, Vaccines (Basel)) - "In light of these results, we are preparing for in vivo vaccination experiments to test the immune focusing properties of this immunogen, the results of which may suggest broad application of the selective avidity concept."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

The Study of Immunization in People Living With HIV Undergoing an ATI for Elicitation of VRC01-lineage Antibodies (clinicaltrials.gov) - P1 | N=35 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Dec 2025 ➔ Oct 2026 | Trial primary completion date: Dec 2025 ➔ Oct 2026 | Suspended ➔ Active, not recruiting

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