{"doi":"10.1101/2022.03.16.484662","title":"A naturally arising broad and potent CD4-binding site antibody with low somatic mutation","abstract":"Abstract The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs exhibit extraordinary breadth and potency, but also rank among the most highly somatically-mutated bNAbs. Here we describe a VRC01-class antibody isolated from a viremic controller, BG24, that has less than half the mutations of most other relatives of its class, while achieving comparable breadth and potency. A 3.8 Å X-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately-mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach. Teaser An anti-HIV-1 antibody with comparable neutralization breadth and potency to similarly-classed antibodies, with half as many mutations.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297670,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":255874,"name":"Till Schoofs","orcid":"0000-0002-3584-8736","position":1,"is_corresponding":false},{"id":16983,"name":"Priyanthi N.P. Gnanapragasam","orcid":null,"position":2,"is_corresponding":false},{"id":896515,"name":"Jovana Golijanin","orcid":null,"position":3,"is_corresponding":false},{"id":16998,"name":"Kathryn E. Huey‐Tubman","orcid":"0000-0002-4683-8138","position":4,"is_corresponding":false},{"id":254286,"name":"Henning Gruell","orcid":"0000-0002-0725-7138","position":5,"is_corresponding":false},{"id":74453,"name":"Philipp Schommers","orcid":"0000-0003-3375-6800","position":6,"is_corresponding":false},{"id":896516,"name":"Nina Suh-Toma","orcid":null,"position":7,"is_corresponding":false},{"id":105101,"name":"Yu E. Lee","orcid":"0000-0001-5989-326X","position":8,"is_corresponding":false},{"id":104705,"name":"Julio C. C. Lorenzi","orcid":"0000-0003-2492-3961","position":9,"is_corresponding":false},{"id":108361,"name":"Alicja Piechocka‐Trocha","orcid":"0000-0002-1547-524X","position":10,"is_corresponding":false},{"id":16967,"name":"Johannes F. Scheid","orcid":"0000-0001-5524-6225","position":11,"is_corresponding":false},{"id":104736,"name":"Anthony P. West","orcid":"0000-0003-4213-5184","position":12,"is_corresponding":false},{"id":108341,"name":"Bruce D. Walker","orcid":"0000-0001-6122-9245","position":13,"is_corresponding":false},{"id":16991,"name":"Michael S. Seaman","orcid":"0000-0001-6444-3562","position":14,"is_corresponding":false},{"id":254287,"name":"Florian Klein","orcid":"0000-0003-1376-1792","position":15,"is_corresponding":false},{"id":104187,"name":"Michel C. Nussenzweig","orcid":"0000-0003-0592-8564","position":16,"is_corresponding":false},{"id":17000,"name":"Pamela J. Björkman","orcid":"0000-0002-2277-3990","position":17,"is_corresponding":false},{"id":16968,"name":"Christopher O. Barnes","orcid":"0000-0003-2754-5951","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:26.161109Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}