ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Antibodies VRC01 and 10E8 neutralize HIV-1 with high breadth and potency even with Ig-framework regions substantially reverted to germline.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 93 citations in OpenAlex.
- The HIV-1 envelope glycoprotein: structure, function and interactions with neutralizing antibodies.Nature reviews. Microbiology · 2025Review
- A comprehensive engineering strategy improves potency and manufacturability of a near pan-neutralizing antibody against HIV.Structure (London, England : 1993) · 2025Article
- Article
- Central tolerance shapes the neutralizing B cell repertoire against a persisting virus in its natural host.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Computational Framework for Determining the Breadth of Antibodies Against Highly Mutable Pathogens.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Somatic Hypermutation and Framework Mutations of Variable Region Contribute to Anti-Zika Virus-Specific Monoclonal Antibody Binding and Function.Journal of virology · 2022Article
- Complementary Roles of Antibody Heavy and Light Chain Somatic Hypermutation in Conferring Breadth and Potency to the HIV-1-Specific CAP256-VRC26 bNAb Lineage.Journal of virology · 2022Article
- Autoreactivity and broad neutralization of antibodies against HIV-1 are governed by distinct mutations: Implications for vaccine design strategies.Frontiers in immunology · 2022Article
- Rapid selection of HIV envelopes that bind to neutralizing antibody B cell lineage members with functional improbable mutations.Cell reports · 2021Article
- Mutational fitness landscapes reveal genetic and structural improvement pathways for a vaccine-elicited HIV-1 broadly neutralizing antibody.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- To bnAb or Not to bnAb: Defining Broadly Neutralising Antibodies Against HIV-1.Frontiers in immunology · 2021Review
- Novel, provable algorithms for efficient ensemble-based computational protein design and their application to the redesign of the c-Raf-RBD:KRas protein-protein interface.PLoS computational biology · 2020Article
- HIV-1 Envelope and MPER Antibody Structures in Lipid Assemblies.Cell reports · 2020Article
- Minimization-Aware RecursiveJournal of computational biology : a journal of computational molecular cell biology · 2020Article
- Chronic Viral Infection Promotes Efficient Germinal Center B Cell Responses.Cell reports · 2020Article
- Cooperation between somatic mutation and germline-encoded residues enables antibody recognition of HIV-1 envelope glycans.PLoS pathogens · 2019Article
- Role of antibody heavy and light chain interface residues in affinity maturation of binding to HIV envelope glycoprotein.Molecular systems design & engineering · 2019Article
- Protein and Glycan Mimicry in HIV Vaccine Design.Journal of molecular biology · 2019Review
- Human Anti-HIV-1 gp120 Monoclonal Antibodies with Neutralizing Activity Cloned from Humanized Mice Infected with HIV-1.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Conjugation of an scFab domain to the oligomeric HIV envelope protein for use in immune targeting.PloS one · 2019Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Abs capable of effectively neutralizing HIV-1 generally exhibit very high levels of somatic hypermutation, both in their CDR and framework-variable regions. In many cases, full reversion of the Ab-framework mutations back to germline results in substantial to complete loss of HIV-1-neutralizing activity. However, it has been unclear whether all or most of the observed framework mutations would be necessary or whether a small subset of these mutations might be sufficient for broad and potent neutralization. To address this issue and to explore the dependence of neutralization activity on the level of somatic hypermutation in the Ab framework, we applied a computationally guided framework-reversion procedure to two broadly neutralizing anti-HIV-1 Abs, VRC01 and 10E8, which target two different HIV-1 sites of vulnerability. Ab variants in which up to 78% (38 of 49 for VRC01) and 89% (31 of 35 for 10E8) of framework mutations were reverted to germline retained breadth and potency within 3-fold of the mature Abs when evaluated on a panel of 21 diverse viral strains. Further, a VRC01 variant with an ∼50% framework-reverted L chain showed a 2-fold improvement in potency over the mature Ab. Our results indicate that only a small number of Ab-framework mutations may be sufficient for high breadth and potency of HIV-1 neutralization by Abs VRC01 and 10E8. Partial framework revertants of HIV-1 broadly neutralizing Abs may present advantages over their highly mutated counterparts as Ab therapeutics and as targets for immunogen design.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.