VRC01 / Acuitas Therap 
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 12 Diseases   6 Trials   6 Trials   384 News 


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  • ||||||||||  VRC01 / Acuitas Therap
    Journal:  Short CDRL1 in intermediate VRC01-like mAbs is not sufficient to overcome key glycan barriers on HIV-1 Env. (Pubmed Central) -  Sep 6, 2024   
    Here we examined whether CDRL1 shortening is a prerequisite for the broadly neutralizing potential of VRC01-class bnAbs, which bind within the CD4 receptor binding site of Env. Our findings indicate that CDRL1 shortening by itself is important but not sufficient for the acquisition of neutralization breadth, and suggest that particular combinations of amino acid mutations, not elicited so far by vaccination, are most likely required for the development of such a feature.
  • ||||||||||  VRC01 / Acuitas Therap
    Eliciting VRC01-class neutralizing antibodies from transgenic mice with low VRC01-class antibody precursor frequency (Poster Exhibition) -  Aug 9, 2024 - Abstract #HIVR4P2024HIVR4P_924;    
    Recruiting --> Active, not recruiting | N=39 --> 13 | Trial completion date: Nov 2029 --> Feb 2025 | Trial primary completion date: Nov 2029 --> Feb 2025 The immunization studies in two stringent VRC01 germline rearranging mouse models identified Mut49 and C13.G4.1-ferritin as better 1st and 2nd immunogens for sequential immunization and demonstrated that these vaccine regimens elicited cross-strain N276 glycan-sensitive serum neutralization, consistent with elicitation of broad VRC01-class nAbs, in a fraction of immunized animals even when the VRC01-class precursor frequency was as low as in humans.
  • ||||||||||  VRC01 / Acuitas Therap
    Discordant VRC01 sensitivity phenotype in participants with HIV-1 multi-lineage infections from the AMP trials (Poster Exhibition) -  Aug 9, 2024 - Abstract #HIVR4P2024HIVR4P_894;    
    We found that during the same transmission event, infection occurred in the treatment arm with both viruses that were highly sensitive to VRC01 and those that were resistant to VRC01. While this suggests that VRC01 provided a selection pressure pre- or post acquisition, other factors including donor virus population and viral fitness may also play a role.
  • ||||||||||  3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, VRC01 / Acuitas Therap
    SERINC5-mediated enhancement of patient-derived envelopes sensitivity to neutralization by bNAbs and autologous plasma antibodies (Poster Exhibition) -  Aug 9, 2024 - Abstract #HIVR4P2024HIVR4P_893;    
    Resultant pseudoviruses were tested for infectivity toward TZM-bl cells in the presence and absence of bNAbs (4E10, 2F5, VRC01 and 3BNC117) and autologous plasma antibodies. The infectivity of all pseudoviruses bearing patient-derived Envelopes was reduced by less than 20% with SERINC5 alone, and neutralized to no more than 60% with bNAbs alone at a concentration of 10
  • ||||||||||  VRC01 / Acuitas Therap
    In vitro affinity maturation of the HIV-1 bnAb N49P7-FR for increased neutralization breadth and potency (Poster Exhibition) -  Aug 9, 2024 - Abstract #HIVR4P2024HIVR4P_790;    
    The infectivity of all pseudoviruses bearing patient-derived Envelopes was reduced by less than 20% with SERINC5 alone, and neutralized to no more than 60% with bNAbs alone at a concentration of 10 Our bnAb optimization campaign maximized the potency and breadth of N49P7-FR, with the created enhanced bnAb variant constituting a promising clinical candidate for future AMP trials and therapeutic regimens.
  • ||||||||||  VRC01 / Acuitas Therap
    High-throughput HIV broadly neutralizing antibody discovery from the United States Military Natural History Study cohort (Poster Exhibition) -  Aug 9, 2024 - Abstract #HIVR4P2024HIVR4P_738;    
    The detection of =75% neutralization breadth in nearly 1 in 10 screened serum samples bodes well for isolating bNAbs from individuals in this cohort. Screening of an additional >700 sera, and confirmation of epitope specificity by functional mapping neutralization assays using epitope mutants will assist in selection of subjects for high-throughput recovery of antibodies.
  • ||||||||||  VRC01 / Acuitas Therap
    Structure of a neutralizing VRC01-class antibody elicited after prime-boost germline-targeting immunization regimen (Cusco Ballroom/Channel 4) -  Aug 9, 2024 - Abstract #HIVR4P2024HIVR4P_321;    
    These findings will help to redefine the immunization regimen to increase HIV neutralization coverage and more efficiently elicit these type of antibodies in future immunization studies. The structure of the G3-1 bound to WT 426c DS.SOSIP can be used to determine why different somatic hypermutations are necessary to become broadly neutralizing.
  • ||||||||||  BG505 GT1.1 gp140 adjuvanted / GSK, IAVI, Rockefeller University, VRC01 / Acuitas Therap
    Induction of precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques following immunization with germline-targeting SOSIP trimers (Cusco Ballroom/Channel 4) -  Aug 9, 2024 - Abstract #HIVR4P2024HIVR4P_226;    
    Infant rhesus macaques (RMs) received either the wild-type (WT) BG505 SOSIP or the CD4bs germline-targeting BG505 GT1.1 SOSIP (n=5/group) with the 3M-052-SE adjuvant at 0, 6, and 12 weeks of age...Most notably, three GT1.1-primed infants exhibited a plasma HIV neutralization signature reflective of VRC01-like CD4bs bnAb precursor development... Thus, a multi-dose immunization regimen with bnAb lineage designed SOSIPs is a promising strategy for implementation in early childhood, and the induction of early B cell responses with the potential to mature into protective HIV bnAbs prior to adolescence when sexual HIV exposure risk begins.
  • ||||||||||  VRC01 / Acuitas Therap
    Defining the contribution of HIV-1 subtype C CD4 binding site mutations to VRC01 resistance and viral fitness (Cusco Ballroom/Channel 4) -  Aug 9, 2024 - Abstract #HIVR4P2024HIVR4P_193;    
    Neutralization resistance of subtype C strains against VRC01 was identified with possible HIV-1 escape sites in the V3 region, gp41 transmembrane and the C2 region. The study confirmed that some mutations found in gp120 significantly contribute to neutralization by the VRC01.Thus investigating resistance mechanisms against VRC01 may shed more light on antibody neutralisation escape of HIV-1.
  • ||||||||||  VRC01 / Acuitas Therap
    Characterization of the B cell repertoire in African populations to inform HIV vaccine design (Cusco Ballroom/Channel 4) -  Aug 9, 2024 - Abstract #HIVR4P2024HIVR4P_151;    
    The study confirmed that some mutations found in gp120 significantly contribute to neutralization by the VRC01.Thus investigating resistance mechanisms against VRC01 may shed more light on antibody neutralisation escape of HIV-1. Despite genetic diversity in the na
  • ||||||||||  VRC01 / Acuitas Therap
    Biodistribution of intra-biliary injected Cu64 labelled HIV bNAbs in a non-human primate model (Limatambo 5/Channel 3) -  Aug 9, 2024 - Abstract #HIVR4P2024HIVR4P_112;    
    Our delivery system of Cu64 via biliary vesicle using NHP models was successful and illustrate a novel mechanism of antibody recirculation and persistence. This delivery approach can be used for a variety of targets in the field of infectious diseases and cancer and will facilitate furthering the HIV therapeutics field.
  • ||||||||||  PGT121 / Gilead, IAVI, VRC01 / Acuitas Therap
    In vitro characterisation of mRNA-mediated delivery of multispecific bNAbs for HIV-1 immunoprophylaxis (Limatambo 5/Channel 3) -  Aug 9, 2024 - Abstract #HIVR4P2024HIVR4P_109;    
    Here we describe the development of in vitro transcribed (IVT)-mRNA delivery of multispecific antibodies as a potential cost-effective, passive immunisation strategy for prevention of HIV-1 acquisition. Previously described tandem single chain variable fragment (scFv) bispecifics (Bi-scFv and Bi-NAb) and heterologous heavy chain (knob-into-hole mutations) assembled tri-specific (Tri-NAb) antibodies combining VRC01/PGT121 and VRC01/PGT121/10e08 paratopes, respectively (>95% neutralisation coverage in vitro (208 pseudovirus panel), with geometric mean IC50 titres <0.4
  • ||||||||||  Potent and broadly neutralizing HIV-1 antibodies with improved pharmacokinetics achieved by negative supercharging (Room 13b/Channel 7) -  Jun 18, 2024 - Abstract #AIDS2024AIDS_3978;    
    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.
  • ||||||||||  VRC01 / Acuitas Therap
    Preclinical, Journal:  mRNA-LNP prime boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models. (Pubmed Central) -  May 16, 2024   
    Boosts drove precursor B cell participation in germinal centers; the accumulation of somatic hypermutations, including in key VRC01-class positions; and affinity maturation to boost and native-like antigens in two of the three precursor lineages. We have preclinically validated a prime-boost regimen of soluble self-assembling nanoparticles encoded by mRNA-LNP, demonstrating that multiple lineages can be primed, boosted, and diversified along the bnAb pathway.
  • ||||||||||  Plasticity of longitudinal antibody immune responses during antiretroviral treatment-na (Poster board: 017) -  May 2, 2024 - Abstract #AIDS2024AIDS_1013;    
    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.
  • ||||||||||  VRC01 / Acuitas Therap
    Human data on CNS penetration by VRC01 in studies from East Africa and Thailand (Room 14a/Channel 9) -  May 2, 2024 - Abstract #AIDS2024AIDS_579;    
    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. Organized by Division of AIDS Research, National Institute of Mental Health
  • ||||||||||  VRC01 / Acuitas Therap
    Enrollment change, Trial completion date, Trial primary completion date:  PET Imaging of Radiolabeled Anti-HIV-1 Envelope Monoclonal Antibody (VRC01) (clinicaltrials.gov) -  Aug 14, 2023   
    P1,  N=30, Recruiting, 
    Trial completion date: Aug 2023 --> Nov 2029 | Trial primary completion date: Aug 2023 --> Nov 2029 N=18 --> 30 | Trial completion date: Oct 2021 --> Jan 2025 | Trial primary completion date: Oct 2021 --> Oct 2024
  • ||||||||||  VRC01 / Acuitas Therap
    Journal:  Adjuvants influence the maturation of VRC01-like antibodies during immunization. (Pubmed Central) -  Nov 22, 2022   
    Here, we examined whether and how three adjuvants, Poly(I:C), GLA-LSQ, or Rehydragel, that activate different pathways of the innate immune system, influence the rate and type of somatic mutations accumulated by VRC01-class BCRs that become activated by the germline-targeting 426c.Mod.Core immunogen and the heterologous HxB2.WT.Core booster immunogen. We report that although the adjuvant used had no influence on the durability of plasma antibody responses after the prime, it influenced the plasma VRC01 antibody titers after the boost and the accumulation of somatic mutations on the elicited VRC01 antibodies.
  • ||||||||||  CAP256V2LS / National Institute of Allergy and Infectious Diseases
    Journal:  Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life. (Pubmed Central) -  Oct 27, 2022   
    The final engineered antibody, CAP256V2LS, retained the extraordinary neutralization potency of the parental antibody, had a favorable pharmacokinetic profile in animal models, and was negative in in vitro assessment of autoreactivity. CAP256V2LS has the requisite potency, developability and suitability for scale-up, allowing its advancement as a clinical candidate.
  • ||||||||||  VRC01 / Acuitas Therap
    Journal:  HIV-1 CD4-binding site germline antibody-Env structures inform vaccine design. (Pubmed Central) -  Oct 25, 2022   
    BG24, a VRC01-class broadly neutralizing antibody (bNAb) against HIV-1 Env with relatively few somatic hypermutations (SHMs), represents a promising target for vaccine strategies to elicit CD4-binding site (CD4bs) bNAbs...In addition, biochemical data and cryo-EM structures of BG24 variants bound to Envs with CD4bs glycans present provide insights into N-glycan accommodation, including structural modes of light chain adaptations in the presence of the N276 glycan. Together, these findings reveal Env regions critical for germline antibody recognition and potential sites to alter in immunogen design.
  • ||||||||||  VRC01 / Acuitas Therap
    Journal:  Engineering the N-glycosylation pathway of Nicotiana tabacum for molecular pharming using CRISPR/Cas9. (Pubmed Central) -  Sep 29, 2022   
    We confirmed full functional knockout of transformants by immunoblotting of total soluble protein by antibodies recognizing β(1,2)-xylose and core α(1,3)-fucose, mass spectrometry analysis of recombinantly produced VRC01, a broadly neutralizing anti-HIV-1 hIgG1 antibody, and Sanger sequencing of targeted regions of the putative transformants. These data represent an important step toward establishing Nicotiana tabacum as a biologics platform for Global Health.
  • ||||||||||  VRC01 / Acuitas Therap
    Biomarker, Journal:  Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition. (Pubmed Central) -  Sep 29, 2022   
    The Antibody Mediated Prevention trials showed that the broadly neutralizing antibody (bnAb) VRC01 prevented acquisition of human immunodeficiency virus-1 (HIV-1) sensitive to VRC01...Based on this result, we suggest that the goal of sustained PT <200 against 90% of circulating viruses can be achieved by promising bnAb regimens engineered for long half-lives. We propose the PT biomarker as a surrogate endpoint for evaluatinon of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines.