ArticleProceedings of the National Academy of Sciences of the United States of America2016
Long antibody HCDR3s from HIV-naïve donors presented on a PG9 neutralizing antibody background mediate HIV neutralization.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- CD98hc-targeted antibody shuttles for central nervous system delivery with broad cross-species reactivity.Nature biomedical engineering · 2026Article
- Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies.The Journal of experimental medicine · 2025Article
- Article
- De Novo Synthesis and Structural Elucidation of CDR-H3 Loop Mimics.ACS chemical biology · 2024Article
- Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies.Nature reviews. Immunology · 2023Review
- Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals.Nature communications · 2022Review
- Review
- Stereotypic neutralizing VScience translational medicine · 2021Article
- To bnAb or Not to bnAb: Defining Broadly Neutralising Antibodies Against HIV-1.Frontiers in immunology · 2021Review
- Discovery of Marburg virus neutralizing antibodies from virus-naïve human antibody repertoires using large-scale structural predictions.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Identification of Structurally Related Antibodies in Antibody Sequence Databases Using Rosetta-Derived Position-Specific Scoring.Structure (London, England : 1993) · 2020Article
- Review
- Cooperation between somatic mutation and germline-encoded residues enables antibody recognition of HIV-1 envelope glycans.PLoS pathogens · 2019Article
- The expanding array of HIV broadly neutralizing antibodies.Retrovirology · 2018Review
- Multiscale Methods in Drug Design Bridge Chemical and Biological Complexity in the Search for Cures.Nature reviews. Chemistry · 2018Article
- Chemo-enzymatic Synthesis of N-glycans for Array Development and HIV Antibody Profiling.Journal of visualized experiments : JoVE · 2018Article
- Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires.Immunity · 2018Article
- How Germinal Centers Evolve Broadly Neutralizing Antibodies: the Breadth of the Follicular Helper T Cell Response.Journal of virology · 2017Article
- Principles of Broad and Potent Antiviral Human Antibodies: Insights for Vaccine Design.Cell host & microbe · 2017Review
- Humanized Immunoglobulin Mice: Models for HIV Vaccine Testing and Studying the Broadly Neutralizing Antibody Problem.Advances in immunology · 2017Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Development of broadly neutralizing antibodies (bnAbs) against HIV-1 usually requires prolonged infection and induction of Abs with unusual features, such as long heavy-chain complementarity-determining region 3 (HCDR3) loops. Here we sought to determine whether the repertoires of HIV-1-naïve individuals contain Abs with long HCDR3 loops that could mediate HIV-1 neutralization. We interrogated at massive scale the structural properties of long Ab HCDR3 loops in HIV-1-naïve donors, searching for structured HCDR3s similar to those of the HIV-1 bnAb PG9. We determined the nucleotide sequences encoding 2.3 × 10(7)unique HCDR3 amino acid regions from 70 different HIV-1-naïve donors. Of the 26,917 HCDR3 loops with 30-amino acid length identified, we tested 30 for further study that were predicted to have PG9-like structure when chimerized onto PG9. Three of these 30 PG9 chimeras bound to the HIV-1 gp120 monomer, and two were neutralizing. In addition, we found 14 naturally occurring HCDR3 sequences that acquired the ability to bind to the HIV-1 gp120 monomer when adding 2- to 7-amino acid mutations via computational design. Of those 14 designed Abs, 8 neutralized HIV-1, with IC50values ranging from 0.7 to 98 µg/mL. These data suggest that the repertoire of HIV-1-naïve individuals contains rare B cells that encode HCDR3 loops that bind or neutralize HIV-1 when presented on a PG9 background with relatively few or no additional mutations. Long HCDR3 sequences are present in the HIV-naïve B-cell repertoire, suggesting that this class of bnAbs is a favorable target for rationally designed preventative vaccine efforts.
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