- |||||||||| Journal: Use of broadly neutralizing antibodies in pediatric HIV for treatment and remission. (Pubmed Central) - Apr 3, 2025
This review synthesizes data for ongoing and planned pediatric bNAb treatment studies, focusing on available trial results that underscore the ability of newer and more potent long-acting bNAbs to sustain viral suppression. We discuss the potential impact of bNAbs to reduce the latent viral reservoir and their use as a strategy to achieve viral remission in children with HIV.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, lefitolimod (MGN1703) / Feng Biosciences, iPharma, Gilead, VRC07-523LS / National Institute of Allergy and Infectious Diseases, IAVI, TaiMed Biologics
Journal: Combination immunotherapy induces post-intervention control of HIV. (Pubmed Central) - Apr 1, 2025
Robust expansion of activated CD8+ T cells early in response to rebounding virus correlated with lower viral load set points. These data suggest that combination immunotherapy approaches might prove effective to induce sustained control of HIV by slowing rebound and improving CD8+ T cell responses, and that these approaches should continue to be optimized.
- |||||||||| VRC01LS / National Institutes of Health, Xencor, 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
Biomarker, Journal: Predictive markers for sustained viral suppression on dual bNAbs during ART interruption in children. (Pubmed Central) - Mar 26, 2025
At the start of bNAb-only treatment, negative qualitative DNA, and especially negative/negative DNA and EIA, have potential to predict maintenance of viral suppression among children on dual bNAbs. HIV RNA target detection below the assay limit did not prove to be a clinically useful biomarker in the visits preceding failure.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
Journal: HIV-Induced Sialoglycans on Infected Cells Promote Immune Evasion from Myeloid Cell-Mediated Killing. (Pubmed Central) - Mar 10, 2025
Treatment with 10-1074-Sia in humanized mice infected with HIV reduces viral load and decreases inflammation. These findings reveal a novel immune evasion mechanism exploited by HIV to evade myeloid cell immune surveillance and highlight the potential of targeting sialoglycan-Siglec interactions to improve immune clearance of HIV-infected cells.
- |||||||||| VRC01LS / National Institutes of Health, Xencor, 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
Immune Correlates of Viral Rebound During Broadly Neutralizing Antibody Treatment in Children (Poster Hall) - Mar 3, 2025 - Abstract #CROI2025CROI_1023;
Conclusions Specific NK cell responses at the beginning of bNAb-only treatment were associated with viral rebound, the kinetics of rebound, and the intact viral reservoir size. HIV-1 specific T cell responses were low in this group of early-treated children and differences could not be identified between controllers and rebounders.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
A Strategy for Durable AAV-Vectored bNAb Expression in Adult Rhesus Macaques (Poster Hall) - Mar 3, 2025 - Abstract #CROI2025CROI_906;
Conclusions We have developed a strategy for sustained bNAb expression in NHPs. This will allow the prophylactic and therapeutic efficacy of AAV-delivered bNAbs to be studied in preclinical NHP models.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, PGDM1400 / National Institute of Allergy and Infectious Diseases, IAVI, VRC01 / Acuitas Therap
Resistance of Inducible, Infectious HIV-1 to Autologous Neutralizing IgG After Long-Term ART (Poster Hall) - Mar 3, 2025 - Abstract #CROI2025CROI_841;
Conclusions Our findings demonstrated increased resistance of outgrowth viruses to aNAbs over long-term ART, which was not fully explained by a decline in neutralizing antibody concentrations. This increased resistance may be driven partially by ADCC-mediated elimination of infected cells carrying aNAb-sensitive viruses, leaving only aNAb-resistant viruses which can contribute to viral rebound.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
Sialidase Conjugation Enhances the Anti-HIV Activity of the 10-1074 Antibody in Humanized Mice (Poster Hall) - Mar 3, 2025 - Abstract #CROI2025CROI_819;
These findings highlight 10-1074-Sia as a promising anti-HIV immunotherapeutic strategy. Further investigation into combining this approach with strategies such as shock-and-kill is warranted to explore its potential for eliminating infected cells during antiretroviral therapy.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
HIV-Induced Sialoglycans on Infected Cells Promote Immune Evasion From Myeloid Cell-Mediated Killing (Poster Hall) - Mar 3, 2025 - Abstract #CROI2025CROI_818;
The HIV-specific antibody 10-1074, conjugated with sialidase (Sia), was employed to disrupt the sialic acid-Siglec interaction specifically on HIV-infected cells...Conclusions We have identified a novel, targetable glyco-immune mechanism through which HIV-infected cells may evade myeloid cell-mediated cytotoxicity by upregulating the expression of specific Siglec ligands. Targeting this interaction presents a promising opportunity for developing innovative immunotherapeutic strategies to eliminate HIV-infected cells.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, Anktiva (nogapendekin alfa inbakicept-pmln) / ImmunityBio
Viral Genetic Traits of Durable Control in Dual Immunotherapy-Treated SHIV-Infected Rhesus Macaques (Poster Hall) - Mar 3, 2025 - Abstract #CROI2025CROI_816;
Observed mutational patterns and glycosylation site disruption likely reflect evolutionary responses to pressure from neutralizing antibodies. Phenotypic characterization of the induced SHIV Env mutants will inform the development of HIV cure approaches.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Sustained T Cell-Mediated Immunity After LS-bNAbs in the RIO Trial: A Vaccinal Effect (Poster Hall) - Mar 3, 2025 - Abstract #CROI2025CROI_453;
At time of submission, there was evidence for an association between baseline CD8+ T cell proliferation to Gag and viral control (HR 1.92; P=0.097), most marked in participants who remained suppressed >15 weeks after bNAb dosing (HR 3.72; P=0.004). Conclusions In RIO, after dosing with two LS-bNAbs and an ATI, there was increased Gag-specific T cell immunity in aviraemic participants which was associated with viral control.
- |||||||||| Intron A (interferon ?-2b) / Merck (MSD), Biogen, 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Time-to-Rebound Measurements in ATI Trials With bNAb Intervention Are Confounded by Autologous NAbs (San Francisco Ballroom C) - Mar 3, 2025 - Abstract #CROI2025CROI_223;
P1
Participants in the NCT03588715 (BEAT2) clinical trial received six infusions of the bNAbs 3BNC117 and 10-1074, and thirty doses of IFNa2b...Higher proportions of replication-competent outgrowth viruses neutralized by aNAbs was associated with a more delayed time-to-rebound following cessation of all immunotherapies. ATI studies must consider the role of pre-existing aNAbs in potentially confounding time-to-rebound measurements.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
HIV-Specific CD8+ T Cell Stemness Predicts Postintervention Control of Viremia (San Francisco Ballroom C) - Mar 3, 2025 - Abstract #CROI2025CROI_220;
Although PIC was not associated with the emergence of new responses or the in vivo activation or expansion of memory responses, modest increases in proliferative capacity and TSCM frequency after bNAb therapy were consistent with a potential vaccinal effect. These results identify functional determinants of PIC that may guide the development of effective immunotherapies to elicit durable ART-free control of viremia in a larger proportion of PWH.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Journal: Comprehensive maps of escape mutations from antibodies 10-1074 and 3BNC117 for Envs from two divergent HIV strains. (Pubmed Central) - Feb 20, 2025
Mutations that escape neutralization by antibody 10-1074 are largely similar for the two Envs, but mutations that escape 3BNC117 differ greatly between Envs. Some differences in the effects of mutations on escape between Envs can be explained by strain-to-strain variation in mutational tolerance or glycosylation patterns, but other mutations have different effects on escape for unclear reasons. Overall, the extent that measurements of mutational effects on antibody neutralization can be generalized across HIV strain differs among antibodies.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
A redesigned HIV-1 Env V1 hypervariable loop renders CRF01_AE Env sensitive to 10-1074 (Poster Exhibition) - Aug 9, 2024 - Abstract #HIVR4P2024HIVR4P_859;
With the motif removed, CRF01_AE Env can be sensitive to 10-1074 in the absence of the 332 glycan. These results highlight that AI-models are valuable tools for vaccine design and that redesigned hypervariable loops can optimize bnAb epitope accessibility on HIV-1 Env antigens.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Imaging of SHIV immune complexes in animal lymph nodes to study T cell priming (Poster Exhibition) - Aug 9, 2024 - Abstract #HIVR4P2024HIVR4P_723;
BACKGROUND: Administration of two HIV-1 Envelope-specific broadly neutralizing antibodies, 3BNC117 and 10-1074, during acute acquisition with an HIV-1 Envelope containing SIV virus (SHIV) resulted in durable CD8+ mediated control of SHIV replication (Nishimura, Nature, 2017). These images are providing a detailed spatiotemporal examination of the host immune response to SHIV VLPs in the context of antibodies, which has the potential to inform the development of novel therapies and vaccines for HIV-1.
- |||||||||| Factors influencing time to viral rebound during analytical treatment interruptions in HIV cure trials (Room 13a/Channel 6) - Jun 18, 2024 - Abstract #AIDS2024AIDS_3973;
The embargo on all abstracts, including oral abstract, poster exhibition, e-poster and late breakers, will lift on Tuesday, 23 July 2024, at 10:00 am Central European Summer Time (CEST). If an abstract is part of an official AIDS 2024 press conference that occurs before that time, the embargo on that abstract lifts at the start of the official press conference.
- |||||||||| UB-421 IV / United BioPharma
Preclinical, Journal, PD(L)-1 Biomarker, IO biomarker: Ex (Pubmed Central) - Jun 16, 2024
Our data suggest that combination therapy with HIV-specific bNAbs and/or UB-421 in the presence of optimized background therapy could potentially provide sustained virologic suppression in PLWH with MDR HIV. However, this therapeutic strategy needs to be evaluated in human clinical trials.
- |||||||||| Improved growth during bNAb-only treatment among early-treated suppressed children with HIV (Poster board: 136) - May 2, 2024 - Abstract #AIDS2024AIDS_1471;
The embargo on all abstracts, including oral abstract, poster exhibition, e-poster and late breakers, will lift on Tuesday, 23 July 2024, at 10:00 am Central European Summer Time (CEST). If an abstract is part of an official AIDS 2024 press conference that occurs before that time, the embargo on that abstract lifts at the start of the official press conference.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
Journal: Caregivers of children with HIV in Botswana prefer monthly IV Broadly Neutralizing Antibodies (bNAbs) to daily oral ART. (Pubmed Central) - Mar 31, 2024
P1/2
Therefore, we emphasise the importance of screening for these mutations before initiating 10-1074 therapy, and to consider the implications of pre-existing resistance when designing prevention strategies. Monthly intravenous bNAb infusions were highly acceptable to caregivers of children with HIV in Botswana and preferred over standard ART by the majority of caregivers.
- |||||||||| PGT121 / Gilead, IAVI, 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Journal: Semen enhances transmitted/founder HIV-1 infection and only marginally reduces antiviral activity of broadly neutralizing antibodies. (Pubmed Central) - Mar 19, 2024
Understanding this interaction is crucial for developing better strategies to prevent HIV-1 transmission. By incorporating the knowledge gained from this study, scientists can now focus on creating microbicides that consider the impact of semen, bringing us closer to more effective prevention methods.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
AAV-Expressed HIV IgG Biologics Enable Durable ART-Free Viral Control in Infant Macaques () - Mar 16, 2024 - Abstract #CROI2024CROI_1201;
Maintenance of virus control required continuous expression of both eCD4-Ig and 10-1074 in plasma at >6.0 ?g/ml. In sum, AAV-vectored delivery of HIV biologics holds promise for achieving sustained virologic remission in CLWH in a practical and scalable manner.
- |||||||||| Intron A (interferon ?-2b) / Merck (MSD), Biogen, 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Autologous Neutralizing Antibodies Contribute to Virus Control in a Subset of PWH Treated With bNAbs () - Mar 16, 2024 - Abstract #CROI2024CROI_1197;
P1
To determine the relative selective pressure of bnAbs and anAbs in the BEAT2 study of 3BNC117, 10-1074, and IFNa2b, we performed a sieve analysis comparing the potency of administered bnAbs and host anAbs against reservoir and rebound Envs.In 8 participants of BEAT2 (NCT03588715), we sequenced provirus from PBMCs collected at study enrollment via FLIPseq or MIPseq (n= 314) to identify intact HIV-1 genomes in single and clonally-expanded populations...In the BEAT2 study of 2 bnAbs and IFNa2b, the greater potency of the administered bnAbs against reservoir vs. rebound Envs indicates bnAb selective pressure. In 2 participants with delayed rebound, baseline anAbs also exerted selective pressure.
- |||||||||| Long Half-Life Broadly Neutralizing Killer Bispecifics Against HIV-1: Harnessing the Immune System (Poster hall) - Mar 16, 2024 - Abstract #CROI2024CROI_1087;
Our data highlights the design and characterization of novel DNA launched immunotherapeutic against HIV-1, which possess significant characteristics of a promising immunotherapy having broad neutralization capacities of a Tier 2/3 global virus panel, specific engagement of effector cells and killing of the infected target cells and longer serum half-life in comparison to conventional bispecific T cell engaging molecules. Delivery of LHL-BnKs as combination therapy
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead, VRC07-523LS / National Institute of Allergy and Infectious Diseases, IAVI, TaiMed Biologics
Post-Intervention HIV Control Linked to Early In Vivo CD8+ T-Cell Proliferative Response to Rebound (Poster hall) - Mar 16, 2024 - Abstract #CROI2024CROI_1052;
P=N/A, P1/
To our knowledge, these studies are the first to demonstrate a relationship between the early in vivo CD8+ T cell proliferative response to viral reactivation and HIV control post-ART. The results support continued focus on developing HIV cure strategies that enhance HIV-specific CD8+ T cell proliferative capacity.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead, VRC07-523LS / National Institute of Allergy and Infectious Diseases, IAVI, TaiMed Biologics
Effect of Broadly Neutralizing Antibody Exposure on HIV Rebound Following Combination Immunotherapy (Poster hall) - Mar 16, 2024 - Abstract #CROI2024CROI_950;
P1/2
Our results suggest that post-treatment setpoint was not driven by bNAb susceptibility and that the association of IQ90 and setpoint is driven by higher VRC07-523LS levels at the time of rebound in those who rebounded earlier and had higher setpoints. Overall, bNAb PK-PD is likely not responsible for lower observed post-treatment setpoints during this trial, suggesting the effect is likely attributable to changes in anti-HIV immune function.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
Discovery of Next-Generation CD4 Mimetic-Based Long-Acting Entry Inhibitors (Poster hall) - Mar 16, 2024 - Abstract #CROI2024CROI_942;
We have successfully engineered CD4 mimetics to prolong their in vivo half-life without affecting antiviral potency. These new constructs are promising candidates as long-acting entry inhibitors for HIV prevention and treatment.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
Preclinical, Journal: In vivo affinity maturation of mouse B cells reprogrammed to express human antibodies. (Pubmed Central) - Mar 15, 2024
Cells edited in this way to express the human immunodeficiency virus type 1 (HIV-1) broadly neutralizing antibody 10-1074 or VRC26.25-y robustly hypermutated and generated potent neutralizing plasma in vaccinated mice...We also used the approach to improve the potency of anti-SARS-CoV-2 antibodies against recent Omicron strains. In vivo affinity maturation of B cells edited at their native loci may facilitate the development of broad, potent and bioavailable antibodies.
- |||||||||| VRC01LS / National Institutes of Health, Xencor, 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
Predictive Markers for Sustained Viral Suppression on Dual bNAbs During ART Interruption in Children (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_344;
Negative qualitative DNA, and especially negative/negative DNA and EIA, at start of bNAb-only treatment predicted maintenance of viral suppression among children on dual bNAbs. HIV-1 RNA target detection below the assay limit did not prove to be a predictive biomarker, and no biomarker combination was clinically useful in the visits preceding failure.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, PGDM1400 / National Institute of Allergy and Infectious Diseases, IAVI
Inducible, Infectious HIV-1 Resistance to Autologous Neutralizing Antibodies After Long-Term ART (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_266;
This suggests a selection process may occur over two decades of ART. These aNAb resistant outgrowth viruses may contribute to viral rebound during treatment interruption, but this data may inform cure strategies with therapeutic vaccines that induce antibodies to neutralization-resistant viruses.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Lower ADCC After 26 Weeks of PEG-IFN-?2b and 2 bNAbs in Otherwise Suppressed HIV-1+ (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_258;
P1
Background: Previous studies suggested that pegylated interferon ?2b (peg-IFN-?2b) and the broadly neutralizing antibodies (bNabs) 3BNC117 and 10-1074 may contribute to cure-related strategies. In PWH, combined immunotherapy with peg-IFN-?2b+bNAbs resulted in no effect on IFN-?-induced NK direct cytotoxicity and an unexpected decrease in gp120-induced ADCC and in circulating CD16+ NK cell subsets.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, VRC07-523LS / National Institute of Allergy and Infectious Diseases, IAVI, TaiMed Biologics
Trial completion date, Trial primary completion date: Safety, Tolerability, and Efficacy of IL-15 Superagonist (N-803) With and Without Combination Broadly Neutralizing Antibodies to Induce HIV-1 Control During Analytic Treatment Interruption (clinicaltrials.gov) - Sep 11, 2023
P1, N=46, Recruiting,
In PWH, combined immunotherapy with peg-IFN-?2b+bNAbs resulted in no effect on IFN-?-induced NK direct cytotoxicity and an unexpected decrease in gp120-induced ADCC and in circulating CD16+ NK cell subsets. Trial completion date: Nov 2024 --> Apr 2026 | Trial primary completion date: Jan 2024 --> Oct 2025
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Trial completion: TITAN: Combining TLR9 Agonist With bNAbs for Reservoir Reduction and Immunological Control of HIV (clinicaltrials.gov) - May 23, 2023
P2a, N=47, Completed,
Future studies using newer bNAb combinations with greater breadth and potency are warranted. Active, not recruiting --> Completed
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
Journal: Complement contributes to antibody-mediated protection against repeated SHIV challenge. (Pubmed Central) - May 12, 2023
Here, functionally modified variants of the second-generation bNAb 10-1074 with ablated and enhanced complement activation profiles were used to examine the role of complement-associated effector functions...Conversely, less bNAb was required to protect animals from plasma viremia when complement activity was enhanced. These results suggest that complement-mediated effector functions contribute to in
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, teropavimab (GS-5423) / Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Evaluation of therapeutic concentrations of anti-HIV antibodies 3BNC117/teropavimab and 10-1074/zinlirvirmab through PK-PD modeling and prediction of the washout duration in HIV cure studies (Poster Exhibition area) - May 5, 2023 - Abstract #IASHIV2023IAS_HIV_467;
These results suggest that complement-mediated effector functions contribute to in Embargoes on oral abstracts and posters lift on Monday, 24 July 2023, at 09:00 Australian Eastern Standard Time (AEST).
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Journal: Vaccinal effect of HIV-1 antibody therapy: dream or reality? (Pubmed Central) - May 5, 2023
HIV-1 bNAbs can enhance adaptive host immune responses in PLWH. The challenge now is to exploit these immunomodulatory properties to design optimized therapeutic interventions to promote and enhance the induction of protective immunity against HIV-1 infection during bNAbs therapy.
- |||||||||| Trogarzo (ibalizumab IV) / Theratechnologies, TaiMed Biologics, 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
Establishing Multilayered Genetic Resistance to HIV-1 by Engineering Hematopoietic Stem and Progenitor Cells for B Cell Specific Secretion of Therapeutic Antibodies (Room 411) - Apr 21, 2023 - Abstract #ASGCT2023ASGCT_1717;
Here, we establish a highly efficient system to simultaneously knock-out CCR5 and knock-in B cell specific antibody expression cassettes in HSPCs to engineer multilayered resistance to HIV-1. We believe this strategy has the potential to become a one-time therapy that leads to long-term control of HIV-1 infection, a disease that currently requires lifetime administration of anti-retroviral therapy to maintain viral suppression.
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