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37 results for “broadly neutralizing antibody”
Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes
<p><strong>Abstract:</strong> Development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 SARS-CoV-2-specific monoclonal Abs (<strong>mAbs</strong>), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an NTD-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy chain-dominant binding pattern seen in other NTD supersite-specific neutralizing Abs with much narrower specificity. We also report the discovery of CC24.2, a pan-sarbecovirus neutralizing antibody that targets a novel RBD epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 protects <i>in vivo</i>, suggesting potential use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design.</p><p><strong>Datasets: </strong>This repository contains the 10x Genomic cellranger outputs (matrix and vdj contig files) as well as complied functional characterization dataset used to generate figures on the publication "Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes". </p><p>Post-vaccination samples for donors CC10, CC25, CC31, CC66 were processed in single 10x Genomic reactions. The timepoints samples consist of multiplexing donors CC10, CC25, CC31, CC66 into one 10x Genomic reaction. Similarly, donors CC26, CC42, CC62, CC67 were multiplexed into a single 10x Genomic reaction.</p><p><strong>Files:</strong></p><p>feature names.csv - csv file with sort bait/antigen barcode key </p><p>feature_reference.csv - csv file with cell hash and antigen barcode reference</p><p>filtered_contig<i>_</i>annotations.csv - High-level annotations of each high-confidence contigs from cell-associated barcodes. This is a subset of all_contig_annotations.csv.</p><p>filtered_contig.fasta - filtered antibody fasta</p><p>filtered_matrix.mtx.gz - 10x Genomic matrix file for filtered cells. Contains counts data for feature and gene expression library.</p><p>raw_matrix.mtx.gz - 10x Genomic matrix file for unfiltered cells. Contains counts data for feature and gene expression library.</p><p><strong>Code: </strong>All code used to generate analysis and figures is available under the MIT license on Github<br> </p>
mRNA prime–boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models
<p>Germline-targeting (GT) protein immunogens to induce VRC01-class broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) of the HIV Envelope have shown promise in clinical trials. Here, we preclinically validated the mRNA-LNP delivery of one such immunogen, eOD-GT8, as a soluble self-assembling 60mer nanoparticle in humanized mouse models. In a model with three humanized B cell lineages bearing distinct VRC01-precursor B cell receptors (BCRs) with similar affinities for eOD-GT8, all lineages could be simultaneously primed and undergo diversification and affinity maturation with no sign of exclusionary competition. 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 delivered by mRNA-LNP, demonstrating that multiple lineages can be primed, boosted, and diversify along the bnAb pathway.</p>
PfRH5-induced human monoclonal antibodies show broadly neutralizing activity in P. falciparum clinical isolates
<p>Vaccines to the <em>Plasmodium falciparum </em>reticulocyte binding-like protein homolog 5 (PfRH5) target the blood stage of the parasite's life cycle. PfRH5 has the potential to trigger the production of strain-transcendent antibodies and has proven its efficacy both in pre-clinical and early clinical studies. Vaccine-induced monoclonal antibodies (mAbs) to PfRH5 showed promising outcomes in cultured <em>P. falciparum </em>strains from distinct geographic areas. Here, we assessed the functional impact of vaccine-induced mAbs to PfRH5 on the genetically more complex <em>P. falciparum </em>clinical isolates. We used mAbs isolated from single-cell sorted B-cells of volunteers enrolled in the phase 1a (NCT02181088) clinical trial of the viral-vectored PfRH5 vaccine and used ex-vivo growth inhibition assays (GIA) to assess their efficacy in <em>P. falciparum </em>clinical isolates. Next-generation sequencing (NGS) was used to assess the breadth of genetic diversity in <em>P. falciparum </em>clinical isolates and to infer the genotype/phenotype relationship involved in antibody susceptibility. We showed a dose-dependent inhibition of clinical isolates with three main GIA groups, high, medium, and low. Except for one isolate, our data shows no significant differences in antibody GIA profile between the <em>P. falciparum </em>clinical isolates and the 3D7 reference strain, which harbours the vaccine allele. We observed an additive relationship, where the combination of GIA-low and GIA-medium antibodies resulted in increased GIA activities, having important implications for the contribution of specific monoclonal antibodies in polyclonal IgG responses. While our NGS analysis showed the occurrence of novel mutations in the <em>pfrh5 </em>gene, these mutations were predicted to have little or no functional impact on the antigen's structure or recognition by known mAbs. Our present findings complement earlier reports on the strain transcendent potential of mAbs to PfRH5 and constitute, to our knowledge, the first report on the susceptibility of <em>P. falciparum </em>clinical isolates from natural infections to vaccine-induced mAbs to PfRH5.</p>
Supplementary Data and Figures for "Myomedin replicas of gp120 V3 loop glycan epitopes of PGT121 and PGT126 antibodies as non-cognate antigens for HIV-1 broadly neutralizing antibodies"
<p>Supplementary pymol sessions for "Myomedin replicas of gp120 V3 loop glycan epitopes of PGT121 and PGT126 antibodies as non-cognate antigens for HIV-1 broadly neutralizing antibodies". Pymol sessions contain the source data for Figure 3, panels A-K.</p>
Safety and Tolerability of AAV8 Delivery of a Broadly Neutralizing Antibody in Adults Living With HIV: a Phase 1, Dose-escalation Trial
ClinicalTrials.gov study NCT03374202. IPD Sharing: NO. Countries: 1. Publications: 3.
PfRH5-induced human monoclonal antibodies show broadly neutralizing activity in P. falciparum clinical isolates
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mRNA prime–boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models
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Converting non-neutralizing SARS-CoV-2 antibodies targeting conserved epitopes into broad-spectrum inhibitors through receptor blockade
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VRC 601: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC HIVMAB060-00-AB (VRC01), With Broad HIV-1 Neutralizing Activity, Administer
ClinicalTrials.gov study NCT01950325. IPD Sharing: Not stated. Countries: 1. Publications: 4.
Safety and Pharmacokinetics of the Combination Broadly Neutralizing Antibodies, 3BNC117-LS-J and 10-1074-LS-J, in Healthy American and African Adults
ClinicalTrials.gov study NCT04173819. IPD Sharing: NO. Countries: 5. Publications: 0.
Peg-Interferon Alpha 2b Combined With Two Intravenous Broadly HIV-1 Neutralizing Antibodies 3BNC117 and 10-1074 (BEAT-2)
ClinicalTrials.gov study NCT03588715. IPD Sharing: NO. Countries: 1. Publications: 5.
Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS), With Broad HIV-1 Neutralizing Activity, Administered Intravenously or Subcutaneously to Healthy Adults
ClinicalTrials.gov study NCT02599896. IPD Sharing: Not stated. Countries: 1. Publications: 4.
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 study NCT04340596. IPD Sharing: YES. Countries: 1. Publications: 0.
A Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission
ClinicalTrials.gov study NCT05719441. IPD Sharing: YES. Countries: 3. Publications: 0.
Broadly Neutralizing Antibodies 3BNC117-LS & 10-1074-LS to Prevent Relapse During ATI
ClinicalTrials.gov study NCT05079451. IPD Sharing: YES. Countries: 1. Publications: 0.
HIV broadly neutralizing antibody precursors induced to the Apex epitope in non-human primates
GEO Series GSE304129. Macaca mulatta. 36 samples. Type: Expression profiling by high throughput sequencing; Other.
Prediction of broadly neutralizing antibodies [BD Rhapsody]
GEO Series GSE229121. Homo sapiens. 2 samples. Type: Expression profiling by high throughput sequencing.
Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies
GEO Series GSE42673. Homo sapiens. 3 samples. Type: Protein profiling by protein array.
Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased binding affinity to Fcg receptors during acute SHIV infection shapes innate and adaptive cellular immunity [set1]
GEO Series GSE254781. Macaca mulatta. 175 samples. Type: Expression profiling by high throughput sequencing.
Simultaneous Induction of Multiple Classes of Broadly Neutralizing Antibody Precursors via Combination Germline-Targeting Immunization
GEO Series GSE306570. Macaca mulatta. 48 samples. Type: Expression profiling by high throughput sequencing; Other.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
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DANDI Archive for NWB datasets
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International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.