{"doi":"10.1126/scitranslmed.ade0424","title":"A prefusion-stabilized RSV F subunit vaccine elicits B cell responses with greater breadth and potency than a postfusion F vaccine","abstract":"There is currently no licensed vaccine for respiratory syncytial virus (RSV). Here, we assess the effect of RSV fusion protein (F) conformation on B cell responses in a post hoc comparison of samples from the DS-Cav1 [prefusion (pre-F)] and MEDI7510 [postfusion (post-F)] vaccine clinical trials. We compared the magnitude and quality of the serological and B cell responses across time points and vaccines. We measured RSV A and B neutralization, F-binding immunoglobulin G titers, and competition assays at week 0 (before vaccination) and week 4 (after vaccination) to evaluate antibody specificity and potency. To compare B cell specificity and activation, we used pre-F and post-F probes in tandem with a 17-color immunophenotyping flow cytometry panel at week 0 (before vaccination) and week 1 (after vaccination). Our data demonstrate that both DS-Cav1 and MEDI7510 vaccination robustly elicit F-specific antibodies and B cells, but DS-Cav1 elicited antibodies that more potently neutralized both RSV A and B. The superior potency was mediated by antibodies that bind antigenic sites on the apex of pre-F that are not present on post-F. In the memory (CD27 + ) B cell compartment, vaccination with DS-Cav1 or MEDI7510 elicited B cells with different epitope specificities. B cells preferentially binding the pre-F probe were activated in DS-Cav1–vaccinated participants but not in MEDI7510-vaccinated participants. Our findings emphasize the importance of using pre-F as an immunogen in humans because of its deterministic role in eliciting highly potent neutralizing antibodies and memory B cells.","journal":"Science Translational Medicine","year":2022,"id":240113,"datarank":1.8049739619599523,"base_score":3.8712010109078907,"endowment":3.8712010109078907,"self_citation_contribution":0.5806801516361837,"citation_network_contribution":1.2242938103237686,"self_endowment_contribution":0.5806801516361837,"citer_contribution":1.2242938103237686,"corpus_percentile":null,"corpus_rank":null,"citation_count":47,"citer_count":43,"citers_with_citation_signal":33,"citers_with_endowment":33,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9669,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02508194","NCT02289820","NCT03049488"]},"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":105590,"name":"Emily Phung","orcid":"0000-0001-9684-9698","position":1,"is_corresponding":false},{"id":234475,"name":"Michelle C. Crank","orcid":null,"position":2,"is_corresponding":false},{"id":105613,"name":"Kaitlyn M. Morabito","orcid":"0000-0002-4849-4690","position":3,"is_corresponding":false},{"id":614534,"name":"Tonya Villafana","orcid":"0000-0001-7929-6374","position":4,"is_corresponding":false},{"id":804745,"name":"Filip Dubovsky","orcid":null,"position":5,"is_corresponding":false},{"id":12091,"name":"Judith Falloon","orcid":"0000-0002-6298-8953","position":6,"is_corresponding":false},{"id":350756,"name":"Mark T. Esser","orcid":"0000-0003-1689-3475","position":7,"is_corresponding":false},{"id":218077,"name":"Bob C. Lin","orcid":"0000-0002-1373-1406","position":8,"is_corresponding":false},{"id":402592,"name":"Grace Chen","orcid":"0000-0001-9236-3180","position":9,"is_corresponding":false},{"id":87311,"name":"Barney S. Graham","orcid":"0000-0001-8112-0853","position":10,"is_corresponding":false},{"id":105610,"name":"Tracy J. Ruckwardt","orcid":"0000-0002-0007-7169","position":11,"is_corresponding":false},{"id":105591,"name":"Lauren A. Chang","orcid":"0000-0002-3287-3987","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T00:22:46.554789Z","pmid":"36542692","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":[]}