{"doi":"10.1101/2024.02.28.582544","title":"Designed mosaic nanoparticles enhance cross-reactive immune responses in mice","abstract":"Summary Using computational methods, we designed 60-mer nanoparticles displaying SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) by ( i ) creating RBD sequences with 6 mutations in the SARS-COV-2 WA1 RBD that were predicted to retain proper folding and abrogate antibody responses to variable epitopes (mosaic-2 COM s; mosaic-5 COM ), and ( ii ) selecting 7 natural sarbecovirus RBDs (mosaic-7 COM ). These antigens were compared with mosaic-8b, which elicits cross-reactive antibodies and protects from sarbecovirus challenges in animals. Immunizations in naïve and COVID-19 pre-vaccinated mice revealed that mosaic-7 COM elicited higher binding and neutralization titers than mosaic-8b and related antigens. Deep mutational scanning showed that mosaic-7 COM targeted conserved RBD epitopes. Mosaic-2 COM s and mosaic-5 COM elicited higher titers than homotypic SARS-CoV-2 Beta RBD-nanoparticles and increased potencies against some SARS-CoV-2 variants than mosaic-7 COM . However, mosaic-7 COM elicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons. These results support using mosaic-7 COM to protect against highly mutated SARS-CoV-2 variants and zoonotic sarbecoviruses with spillover potential.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485957,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"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":16982,"name":"Alexander A. Cohen","orcid":"0000-0002-2818-656X","position":1,"is_corresponding":false},{"id":1064499,"name":"Luis F. Caldera","orcid":"0009-0005-3254-6563","position":2,"is_corresponding":false},{"id":16970,"name":"Jennifer R. Keeffe","orcid":"0000-0002-5317-6398","position":3,"is_corresponding":false},{"id":1204088,"name":"Annie V. Rorick","orcid":"0009-0003-1801-6940","position":4,"is_corresponding":false},{"id":1329822,"name":"Yusuf M. Aida","orcid":null,"position":5,"is_corresponding":false},{"id":16983,"name":"Priyanthi N.P. Gnanapragasam","orcid":null,"position":6,"is_corresponding":false},{"id":17000,"name":"Pamela J. Björkman","orcid":"0000-0002-2277-3990","position":7,"is_corresponding":false},{"id":110109,"name":"Arup K. Chakraborty","orcid":"0000-0003-1268-9602","position":8,"is_corresponding":false},{"id":308075,"name":"Eric Wang","orcid":"0000-0003-0330-0597","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T02:07:57.049469Z","pmid":"38464322","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":[]}