{"doi":"10.1101/2021.11.02.466200","title":"Neutralizing antibodies induced in immunized macaques recognize the CD4-binding site on an occluded-open HIV-1 envelope trimer","abstract":"Abstract Broadly-neutralizing antibodies (bNAbs) against HIV-1 Env can protect from infection. We characterize Ab1303 and Ab1573, heterologously-neutralizing CD4-binding site (CD4bs) antibodies, isolated from sequentially-immunized macaques. Ab1303/Ab1573 binding is observed only when Env trimers are not constrained in the closed, prefusion conformation. Fab-Env cryo-EM structures show that both antibodies recognize the CD4bs on Env trimer with an ‘occluded-open’ conformation between closed, as targeted by bNAbs, and fully-open, as recognized by CD4. The occluded-open Env trimer conformation includes outwardly-rotated gp120 subunits, but unlike CD4-bound Envs, does not exhibit V1V2 displacement, 4-stranded gp120 bridging sheet, or co-receptor binding site exposure. Inter-protomer distances within trimers measured by double electron-electron resonance spectroscopy suggest an equilibrium between occluded-open and closed Env conformations, consistent with Ab1303/Ab1573 binding stabilizing an existing conformation. Studies of Ab1303/Ab1573 demonstrate that CD4bs neutralizing antibodies that bind open Env trimers can be raised by immunization, thereby informing immunogen design and antibody therapeutic efforts.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":215245,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9644,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105096,"name":"Kim-Marie A. Dam","orcid":"0000-0002-1416-4757","position":1,"is_corresponding":false},{"id":809950,"name":"Michael D. Bridges","orcid":"0000-0001-9999-9106","position":2,"is_corresponding":false},{"id":107613,"name":"Magnus A. G. Hoffmann","orcid":"0000-0003-4923-9568","position":3,"is_corresponding":false},{"id":618794,"name":"Andrew T. DeLaitsch","orcid":"0000-0002-3458-3449","position":4,"is_corresponding":false},{"id":105098,"name":"Harry B. Gristick","orcid":"0000-0002-1957-2821","position":5,"is_corresponding":false},{"id":240117,"name":"Amelia Escolano","orcid":"0000-0002-1945-2440","position":6,"is_corresponding":false},{"id":353336,"name":"Rajeev Gautam","orcid":"0000-0003-2390-8727","position":7,"is_corresponding":false},{"id":371016,"name":"Malcolm A. Martin","orcid":"0000-0003-1232-2966","position":8,"is_corresponding":false},{"id":104187,"name":"Michel C. Nussenzweig","orcid":"0000-0003-0592-8564","position":9,"is_corresponding":false},{"id":317676,"name":"Wayne L. Hubbell","orcid":"0000-0003-0577-3312","position":10,"is_corresponding":false},{"id":17000,"name":"Pamela J. Björkman","orcid":"0000-0002-2277-3990","position":11,"is_corresponding":false},{"id":614448,"name":"Zhi Yang","orcid":"0000-0001-8680-3784","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T23:52:55.971300Z","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":[]}