{"doi":"10.1101/2023.08.21.554179","title":"Heterologous sarbecovirus receptor binding domains as scaffolds for SARS-CoV-2 receptor binding motif presentation","abstract":"Structure-guided rational immunogen design can generate optimized immunogens that elicit a desired humoral response. Design strategies often center upon targeting conserved sites on viral glycoproteins that will ultimately confer potent neutralization. For SARS-CoV-2 (SARS-2), the surface-exposed spike glycoprotein includes a broadly conserved portion, the receptor binding motif (RBM), that is required to engage the host cellular receptor, ACE2. Expanding humoral responses to this site may result in a more potently neutralizing antibody response against diverse sarbecoviruses. Here, we used a \"resurfacing\" approach and iterative design cycles to graft the SARS-2 RBM onto heterologous sarbecovirus scaffolds. The scaffolds were selected to vary the antigenic distance relative to SARS-2 to potentially focus responses to RBM. Multimerized versions of these immunogens elicited broad neutralization against sarbecoviruses in the context of preexisting SARS-2 immunity. These validated engineering approaches can help inform future immunogen design efforts for sarbecoviruses and are generally applicable to other viruses.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":410719,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":239721,"name":"Maya Sangesland","orcid":"0000-0001-8316-039X","position":1,"is_corresponding":false},{"id":108252,"name":"Evan C. Lam","orcid":"0000-0002-5556-2559","position":2,"is_corresponding":false},{"id":614444,"name":"Kerri St. Denis","orcid":"0000-0002-6324-7890","position":3,"is_corresponding":false},{"id":804625,"name":"Maegan L. Sheehan","orcid":null,"position":4,"is_corresponding":false},{"id":1178968,"name":"Mya Vu","orcid":null,"position":5,"is_corresponding":false},{"id":1190970,"name":"Agnes H. Cheng","orcid":null,"position":6,"is_corresponding":false},{"id":108262,"name":"Alejandro B. Balazs","orcid":"0000-0002-1767-3944","position":7,"is_corresponding":false},{"id":104358,"name":"Daniel Lingwood","orcid":"0000-0001-5631-9238","position":8,"is_corresponding":false},{"id":104357,"name":"Aaron G. Schmidt","orcid":"0000-0003-3627-2553","position":9,"is_corresponding":false},{"id":104324,"name":"Blake M. Hauser","orcid":"0000-0002-0100-1684","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:21:35.071397Z","pmid":"37662405","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":[]}