{"doi":"10.1101/2022.03.25.485873","title":"HIV-1 CD4-binding site germline antibody–Env structures inform vaccine design","abstract":"Abstract BG24, a VRC01-class broadly neutralizing antibody (bNAb) against HIV-1 Env with relatively few somatic hypermutations (SHMs), represents a promising target for vaccine strategies to elicit CD4-binding site (CD4bs) bNAbs. To understand how SHMs correlate with BG24 neutralization of HIV-1, we solved 4.1 Å and 3.4 Å single-particle cryo-EM structures of two inferred germline (iGL) BG24 precursors complexed with engineered Env-based immunogens lacking CD4bs N-glycans. Structures revealed critical Env contacts by BG24 iGL and identified antibody light chain structural features that impede Env recognition. In addition, biochemical data and cryo-EM structures of BG24 iGL variants bound to Envs with CD4bs glycans present provided insights into N-glycan accommodation, including structural modes of light chain adaptations in the presence of the N276 gp120 glycan. Together, these findings revealed Env regions critical for germline antibody recognition and potential sites to alter in immunogen design.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":301073,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"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":16968,"name":"Christopher O. Barnes","orcid":"0000-0003-2754-5951","position":1,"is_corresponding":false},{"id":105098,"name":"Harry B. Gristick","orcid":"0000-0002-1957-2821","position":2,"is_corresponding":false},{"id":255874,"name":"Till Schoofs","orcid":"0000-0002-3584-8736","position":3,"is_corresponding":false},{"id":104187,"name":"Michel C. Nussenzweig","orcid":"0000-0003-0592-8564","position":4,"is_corresponding":false},{"id":17000,"name":"Pamela J. Björkman","orcid":"0000-0002-2277-3990","position":5,"is_corresponding":false},{"id":105096,"name":"Kim-Marie A. Dam","orcid":"0000-0002-1416-4757","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T00:31:57.812980Z","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":[]}