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


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  • ||||||||||  VRC01 / Acuitas Therap
    Journal:  A Novel Anti-HIV-1 Bispecific bNAb-Lectin Fusion Protein Engineered in a Plant-based Transient Expression System. (Pubmed Central) -  Mar 3, 2020   
    Notably, VRC01 -Avaren showed significantly stronger neutralizing effects than the bivalent parent molecules VRC01 IgG and Avaren-Fc, with IC values ranging from 48 to 310 pM. These results support the continued development of bispecific anti-HIV proteins based on Avaren and bNAbs, to which plant-based transient overexpression systems will provide an efficient protein engineering and production platform.
  • ||||||||||  VRC01 / Acuitas Therap
    [VIRTUAL] A PHASE I DOSE-ESCALATION TRIAL OF HUMAN MONOCLONAL ANTIBODY N6LS IN HEALTHY ADULTS ([VIRTUAL]) -  Mar 2, 2020 - Abstract #CROI2020CROI_1223;    
    N6LS targets the CD4-binding site (CD4bs) of the HIV-1 envelope glycoprotein and is a member of the VRC01 class of CD4bs antibodies...N6LS was safe and well tolerated by IV and SC administration and displayed encouraging PK parameters. Given its high neutralization breadth and potency, N6LS is a promising candidate for inclusion in HIV-1 prevention and therapeutic strategies.
  • ||||||||||  PGT121 / Theraclone Sciences, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotechnologies, VRC01 / Acuitas Therap
    [VIRTUAL] HIV-1 ENVELOPES FROM PERSISTENT VIREMIA ON ART SHOW REDUCED ANTIBODY SENSITIVITY ([VIRTUAL]) -  Mar 2, 2020 - Abstract #CROI2020CROI_1195;    
    Of the 16 mAbs tested, only 3BNC117 and 10e8 potently neutralized all the PSVs. Plasma-derived Envs from individuals with persistent viremia on ART exhibit reduced sensitivity to mAbs targeting CD4bs, Gp41, and Apex, compared to tier 1 and 2 Envs. 3BNC117 and 10e8, however, neutralized all PSVs assayed, indicating therapeutic potential for clearing persistent viremia in the individuals studied.
  • ||||||||||  VRC01 / Acuitas Therap
    [VIRTUAL] THE HIV ANTISENSE PROTEIN ASP IS A TRANSMEMBRANE PROTEIN OF THE VIRAL ENVELOPE ([VIRTUAL]) -  Mar 2, 2020 - Abstract #CROI2020CROI_1130;    
    Indeed, 324.6 captured HIV-1 particles with efficiency similar to anti-gp120 VRC01...Knocking out ASP expression reduced viral replication. Preservation or restoration of functional ASP ORF during natural infection indicates that ASP may provide a selective advantage to HIV-1.
  • ||||||||||  Selzentry (maraviroc) / ViiV Healthcare, PGT121 / Theraclone Sciences, VRC01 / Acuitas Therap
    [VIRTUAL] GENETIC IDENTITY AND BIOLOGICAL PHENOTYPE OF EARLY TRANSMITTED FOUNDER HIV-1 VIRUSES ([VIRTUAL]) -  Mar 2, 2020 - Abstract #CROI2020CROI_1128;    
    65 out of 250 clones tested were found infectious and analyzed for genetic identity and biological phenotype of virus variants such as per-particle infectivity, response to neutralizing antibody (nAb), Maraviroc (MVC) and Interferon alpha (IFN-a)...The sensitivity of the TF variants to MVC and a standard panel of nAbs (VRC01, PG09, PG16, and PGT121) were found to be much lower in TF than NT variants...Despite small sample size, the study identified precise molecular and biological phenotype of the TF viral strains and its evolutionary dynamics on transmission-associated bottlenecks. In general, these studies improve our knowledge about the very diverse and highly adaptable nature of the TF virus, and hopefully takes us a few steps closer to addressing the challenges that come in the way of developing an effective vaccine or cure against HIV-1 infection.
  • ||||||||||  [VIRTUAL] SAFETY AND PHARMACOKINETICS OF INTRAVENOUS VRC01LS AND 10-1074 IN YOUNG CHILDREN ([VIRTUAL]) -  Mar 2, 2020 - Abstract #CROI2020CROI_864;    
    Early-treated HIV+ children may be ideal candidates for use of broadly neutralizing monoclonal antibodies (bNAbs) as an alternative to antiretroviral treatment (ART), but pediatric bNAb data to date has been limited to subcutaneous administration of VRC01/LS during infancy...All children were receiving lopinavir/ritonavir, zidovudine, lamivudine (and one was also on abacavir)...For VRC01LS, an increased maintenance dose of at least 15mg/kg may be needed to achieve concentrations similar to adults when dosed monthly. For 10-1074, predicted adult concentrations were slightly exceeded with 30mg/kg monthly.
  • ||||||||||  VRC01 / Acuitas Therap
    [VIRTUAL] INFILTRATION OF bNAb VRC01 INTO THE CEREBROSPINAL FLUID IN HUMANS IN THE RV397 STUDY ([VIRTUAL]) -  Mar 2, 2020 - Abstract #CROI2020CROI_852;    
    The bioavailability of this potent and broad HIV monoclonal antibody in the CNS is critical considering that the CNS can facilitate the generation of resistant HIV quasi-species that are distinct from virus in systemic circulation. These results thus serve to inform the design of immunotherapies to target HIV infection in the CNS.
  • ||||||||||  VRC01 / Acuitas Therap
    [VIRTUAL] WHOLE-BODY PET IMAGING OF THE HIV RESERVOIR USING RADIOLABELED VRC01 ([VIRTUAL]) -  Mar 2, 2020 - Abstract #CROI2020CROI_228;    
    Importantly, PET tracer uptake correlated with measures of HIV protein expression in tissue. These data suggest that PET imaging of HIV-infected cells has the potential to localize and quantify multiple anatomical HIV reservoirs in a wide range of HIV persistence and curative studies.
  • ||||||||||  VRC01 / Acuitas Therap
    Trial completion date, Trial primary completion date:  Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women (clinicaltrials.gov) -  Feb 28, 2020   
    P2b,  N=1900, Active, not recruiting, 
    These data suggest that PET imaging of HIV-infected cells has the potential to localize and quantify multiple anatomical HIV reservoirs in a wide range of HIV persistence and curative studies. Trial completion date: Sep 2020 --> Dec 2020 | Trial primary completion date: Sep 2020 --> Dec 2020
  • ||||||||||  VRC01 / Acuitas Therap
    At-line nutrient profiling from cell media in 7 minutes with a new integrated analyzer (Exhibit Hall D, Pennsylvania Convention Center) -  Feb 13, 2020 - Abstract #ACSSp2020ACS_Sp_13477;    
    Finally, the analyzer was tested doing spent media analysis of a batch fed process of CHO NIH VRC01 cell line grown under different ammonia stress concentrations on an ambr®250...Other media components either steadily decreased in concentration or were completely depleted by the end of culture. In the future, the rapid analysis capability of the analyzer combined with the low sample volume requirements would allow for more frequent spent media analysis to occur for real-time observation of these process changes and associated control strategies.
  • ||||||||||  VRC01 / Acuitas Therap
    Impact of ammonia stress on glycosylation of the VRC01 monoclonal antibody produced in CHO cells (Exhibit Hall D, Pennsylvania Convention Center) -  Feb 13, 2020 - Abstract #ACSSp2020ACS_Sp_13388;    
    We found that increased ammonia concentrations measured in the culture for all conditions tested led to a decrease in total and terminal galactosylation, as well as a decrease in sialylation of the associated glycans. Future work will look into how the conserved Asn297 Fc glycan is impacted compared to Fab glycans under various culturing conditions.
  • ||||||||||  VRC01 / Acuitas Therap
    Trial completion date, Trial primary completion date:  PET Imaging of Radiolabeled Anti-HIV-1 Envelope Monoclonal Antibody (VRC01) (clinicaltrials.gov) -  Feb 5, 2020   
    P1,  N=18, Recruiting, 
    Future work will look into how the conserved Asn297 Fc glycan is impacted compared to Fab glycans under various culturing conditions. Trial completion date: Oct 2019 --> Oct 2020 | Trial primary completion date: Oct 2019 --> Oct 2020
  • ||||||||||  VRC01 / Acuitas Therap
    Journal:  Delayed vaginal SHIV infection in VRC01 and anti-α4β7 treated rhesus macaques. (Pubmed Central) -  Nov 21, 2019   
    The combination of suboptimal amounts of VRC01 and Rh-α4β7 delayed infection, altered antiviral immune responses and minimized CD4+ T cell loss. Further exploration of the effect of combining bNAbs with Rh-α4β7 on SIV/HIV infection and antiviral immune responses is warranted and may lead to novel preventive and therapeutic strategies.
  • ||||||||||  VRC01 / Acuitas Therap
    Novel highly potent CD4bs bNAb with restricted pathway to HIV-1 escape (Darwin) -  Nov 15, 2019 - Abstract #EACS2019EACS_2226;    
    Further exploration of the effect of combining bNAbs with Rh-α4β7 on SIV/HIV infection and antiviral immune responses is warranted and may lead to novel preventive and therapeutic strategies. 1-18 is a highly potent and broad bNAb that restricts escape and overcomes frequent CD4bs escape pathways, providing new options for bNAb combinations to prevent and treat HIV-1 infection.
  • ||||||||||  VRC01 / National Institute of Allergy and Infectious Diseases
    Journal:  Structural Rearrangements Maintain the Glycan Shield of an HIV-1 Envelope Trimer After the Loss of a Glycan. (Pubmed Central) -  Oct 31, 2019   
    We examined a naturally occurring subtype C isolate and its N301A mutant; the mutant not only remained protected against neutralising antibodies targeting underlying epitopes, but also exhibited an increased resistance to the VRC01 class of broadly neutralising antibodies...These data provide detailed insight into the glycan shield's ability to compensate for the loss of a glycan, as well as the cascade of glycan movements on a protomer, starting at the point mutation, that affects the integrity of an antibody epitope located at the edge of the diminishing effect. These results present key, previously overlooked, considerations for HIV-1 Env glycan research and related vaccine studies.
  • ||||||||||  PGT121 / Theraclone Sciences, 3BNC117 / Rockefeller University, Cornell University, VRC01 / National Institute of Allergy and Infectious Diseases
    Journal:  Sensitivity to Broadly Neutralizing Antibodies of Recently Transmitted HIV-1 Clade CRF02_AG Viruses with a Focus on Evolution over Time. (Pubmed Central) -  Oct 24, 2019   
    We observed a higher resistance to bnAbs targeting the V1V2-glycan region (PG9 and PGT145) and the V3-glycan region (PGT121 and 10-1074)...We evaluated their sensitivity to bnAbs, including those the most advanced in clinical trials, and looked for the best combinations. In addition, we observed a trend toward increased resistance to bnAbs over the course of the epidemic.
  • ||||||||||  VRC01 / National Institute of Allergy and Infectious Diseases
    Journal:  A systematic analysis of VRC01 antibody expression in Pichia pastoris through signal peptide optimization. (Pubmed Central) -  Oct 9, 2019   
    Interestingly it was determined that the highest yields were achieved when the murine IgG1 signal peptide was fused to the light chain, with several different signal peptides leading to high yield when fused to the heavy chain. Finally, we have evaluated the effect of using a 2A signal peptide to create a bicistronic vector in the attempt to reduce burden and increase transformation efficiency, but found it to give reduced yields compared to using two independent vectors.
  • ||||||||||  VRC01 / National Institute of Allergy and Infectious Diseases
    Journal:  The human naive B cell repertoire contains distinct subclasses for a germline-targeting HIV-1 vaccine immunogen. (Pubmed Central) -  Oct 9, 2019   
    These different subclasses within the human repertoire had strong initial affinities (K) to the immunogen, up to 13 nM, and represent encouraging indications that multiple independent pathways may exist for vaccine-elicited VRC01-class bnAb development in most individuals. The frequencies of these distinct eOD-GT8 B cell specificities give insights into antigen-specific compositional features of the human naive B cell repertoire and provide actionable information for vaccine design and advancement.
  • ||||||||||  VRC01 / National Institute of Allergy and Infectious Diseases
    Journal:  HIV-1 latent reservoir size and diversity are stable following brief treatment interruption. (Pubmed Central) -  Sep 18, 2019   
    P1
    The frequencies of these distinct eOD-GT8 B cell specificities give insights into antigen-specific compositional features of the human naive B cell repertoire and provide actionable information for vaccine design and advancement. The results indicate that transient viremia from ATI does not substantially alter measures of the latent reservoir, that clonal expansion is prevalent within the latent reservoir, and that characterization of latent viruses that can reactivate in vivo remains challenging.
  • ||||||||||  VRC01 / Acuitas Therap
    Journal:  Flow virometric sorting and analysis of HIV quasispecies from plasma. (Pubmed Central) -  Jun 15, 2019   
    Importantly, using two broadly neutralizing HIV antibodies, PG9 and VRC01, we also sorted virus from archived human plasma and analyzed the sorted populations genetically and by proteomics, identifying the quasispecies present. The ability to sort infectious HIV from clinically relevant samples provides material for detailed molecular, genetic, and proteomic analyses applicable to future design of vaccine antigens and potential development of personalized treatment regimens.
  • ||||||||||  VRC01 / National Institute of Allergy and Infectious Diseases
    Clinical, Journal:  Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity. (Pubmed Central) -  Jun 11, 2019   
    Almost all viruses from the plasmas were neutralization-resistant to VRC01 and A7 lineage antibodies. For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
  • ||||||||||  VRC01 / National Institute of Allergy and Infectious Diseases
    Preclinical, Journal:  CRISPR/Cas9 gene editing for the creation of an MGAT1-deficient CHO cell line to control HIV-1 vaccine glycosylation. (Pubmed Central) -  Jun 4, 2019   
    Monomeric gp120s produced in the MGAT1- CHO cell line exhibit improved binding to prototypic glycan-dependent bN-mAbs directed to the V1/V2 domain (e.g., PG9) and the V3 stem (e.g., PGT128 and 10-1074) while preserving the structure of the important glycan-independent epitopes (e.g., VRC01). The ability of the MGAT1- CHO cell line to limit glycosylation to early intermediates in the N-linked glycosylation pathway without impairing the doubling time or ability to grow at high cell densities suggests that it will be a useful substrate for the biopharmaceutical production of HIV-1 vaccine immunogens.
  • ||||||||||  VRC01 / National Institute of Allergy and Infectious Diseases
    Journal:  Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. (Pubmed Central) -  May 29, 2019   
    Early mutations defined maturation pathways toward limited or broad neutralization, suggesting that focusing the immune response is likely required to steer B cell maturation toward the development of neutralization breadth. Finally, VRC01 lineage bnAbs with long CDR H3s overcame the HIV-1 N276 glycan barrier without shortening their CDR L1, revealing a solution for broad neutralization in which the heavy chain, not CDR L1, is the determinant to accommodate the N276 glycan.
  • ||||||||||  VRC01 / National Institute of Allergy and Infectious Diseases
    Journal:  Prediction of VRC01 neutralization sensitivity by HIV-1 gp160 sequence features. (Pubmed Central) -  May 24, 2019   
    Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis. This modeling framework may also inform the study of VRC01 in the treatment of HIV-infected persons.
  • ||||||||||  VRC01 / National Institute of Allergy and Infectious Diseases
    Clinical, P2b data, Journal:  Modeling Cumulative Overall Prevention Efficacy for the VRC01 Phase 2b Efficacy Trials. (Pubmed Central) -  May 7, 2019   
    Given the lack of available knowledge and data to verify the assumptions undergirding our modeling framework, its quantitative predictions of overall PE are preliminary. Its current main applications are to supplement decisions to advance mAb regimens to efficacy trials, and to enable mAb regimen ranking by their potential for PE in humans.
  • ||||||||||  VRC01 / National Institute of Allergy and Infectious Diseases
    Clinical, Journal:  The adjuvant AlhydroGel elicits higher antibody titres than AddaVax when combined with HIV-1 subtype C gp140 from CAP256. (Pubmed Central) -  May 7, 2019   
    ...Lectin affinity purified soluble Env protein was mainly trimeric as judged by molecular weight using BN-PAGE and contained intact broadly neutralising epitopes for the V3-glycan supersite (monoclonal antibodies PGT128 and PGT135), the CD4 binding site (VRC01) and the V2-glycan (PG9) but not for the trimer-specific monoclonal antibodies PG16, PGT145 and CAP256-VRC26_08...These data suggest that adjuvant selection is critical for developing a successful vaccine and AlhydroGel should be further investigated. Additional purification of trimeric native-like CAP256 Env and/or priming with DNA or MVA might enhance the induction of neutralizing antibodies and possible Tier 2 HIV-1 neutralisation.
  • ||||||||||  VRC01 / National Institute of Allergy and Infectious Diseases
    Journal, Monotherapy:  Monotherapy with a low-dose lipopeptide HIV fusion inhibitor maintains long-term viral suppression in rhesus macaques. (Pubmed Central) -  Apr 11, 2019   
    ...It inhibited a large panel of divergent HIV subtypes with a mean IC50 in the extremely low picomolar range, being > 5,300-fold more active than T-20 and the neutralizing antibody VRC01...In the monkey, subcutaneous administration of 3 mg/kg LP-80 yielded serum concentrations of 1,147 ng/ml after injection 72 h and 9 ng/ml after injection 168 h (7 days), equivalent to 42,062- and 330-fold higher than the measured IC50 value. In SHIV infected rhesus macaques, a single low-dose LP-80 (3 mg/kg) sharply reduced viral loads to below the limitation of detection, and twice-weekly monotherapy could maintain long-term viral suppression.
  • ||||||||||  VRC01 / National Institute of Allergy and Infectious Diseases
    Journal:  Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies. (Pubmed Central) -  Mar 27, 2019   
    Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G B cells including VRC01-class precursors. These results demonstrate that glycan masking can limit elicitation of off-target antibodies and focus immune responses to the CD4bs, a major target of HIV-1 vaccine design.