{"doi":"10.3389/fimmu.2024.1484029","title":"Vaccine-elicited and naturally elicited antibodies differ in their recognition of the HIV-1 fusion peptide","abstract":"Broadly neutralizing antibodies have been proposed as templates for HIV-1 vaccine design, but it has been unclear how similar vaccine-elicited antibodies are to their naturally elicited templates. To provide insight, here we compare the recognition of naturally elicited and vaccine-elicited antibodies targeting the HIV-1 fusion peptide, which comprises envelope (Env) residues 512-526, with the most common sequence being AVGIGAVFLGFLGAA. Naturally elicited antibodies bound peptides with substitutions to negatively charged amino acids at residue positions 517-520 substantially better than the most common sequence, despite these substitutions rarely appearing in HIV-1; by contrast, vaccine-elicited antibodies were less tolerant of sequence variation, with no substitution of residues 512-516 showing increased binding. Molecular dynamics analysis and cryo-EM structural analysis of the naturally elicited ACS202 antibody in complex with the HIV-1 Env trimer with an alanine 517 to glutamine substitution suggested enhanced binding to result from electrostatic interactions with positively charged antibody residues. Overall, vaccine-elicited antibodies appeared to be more fully optimized to bind the most common fusion peptide sequence, perhaps reflecting the immunization with fusion peptide of the vaccine-elicited antibodies.","journal":"Frontiers in Immunology","year":2024,"id":482219,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":323756,"name":"Kai Xu","orcid":"0000-0001-5412-6942","position":1,"is_corresponding":false},{"id":615584,"name":"Myungjin Lee","orcid":"0000-0002-4972-3811","position":2,"is_corresponding":false},{"id":229157,"name":"Shuishu Wang","orcid":"0000-0002-0865-4522","position":3,"is_corresponding":false},{"id":229155,"name":"Adam S. Olia","orcid":"0000-0003-0805-1331","position":4,"is_corresponding":false},{"id":842011,"name":"Darcy R. Harris","orcid":"0000-0002-3671-6452","position":5,"is_corresponding":false},{"id":560488,"name":"Kevin Liu","orcid":"0000-0002-0942-6513","position":6,"is_corresponding":false},{"id":622891,"name":"Tracy Liu","orcid":"0000-0003-0671-8390","position":7,"is_corresponding":false},{"id":439616,"name":"Andrew J. Schaub","orcid":"0000-0001-7770-7045","position":8,"is_corresponding":false},{"id":229982,"name":"Tyler Stephens","orcid":null,"position":9,"is_corresponding":false},{"id":695488,"name":"Yiran Wang","orcid":"0009-0007-3244-3534","position":10,"is_corresponding":false},{"id":229158,"name":"Baoshan Zhang","orcid":"0000-0002-0165-1513","position":11,"is_corresponding":false},{"id":422735,"name":"Rick Huang","orcid":"0000-0002-3336-9635","position":12,"is_corresponding":false},{"id":229148,"name":"Yaroslav Tsybovsky","orcid":"0000-0002-2159-5248","position":13,"is_corresponding":false},{"id":105633,"name":"Peter D. Kwong","orcid":"0000-0003-3560-232X","position":14,"is_corresponding":false},{"id":323754,"name":"Reda Rawi","orcid":"0000-0002-0445-2325","position":15,"is_corresponding":false},{"id":664335,"name":"Mateo Reveiz","orcid":null,"position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:07:14.349221Z","pmid":"39611147","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":[]}