{"doi":"10.1101/2020.11.18.388934","title":"An engineered receptor-binding domain improves the immunogenicity of multivalent SARS-CoV-2 vaccines","abstract":"ABSTRACT The SARS-coronavirus 2 (SARS-CoV-2) spike (S) protein mediates viral entry into cells expressing the angiotensin-converting enzyme 2 (ACE2). The S protein engages ACE2 through its receptor-binding domain (RBD), an independently folded 197-amino acid fragment of the 1273-amino acid S-protein protomer. The RBD is the primary SARS-CoV-2 neutralizing epitope and a critical target of any SARS-CoV-2 vaccine. Here we show that this RBD conjugated to each of two carrier proteins elicited more potent neutralizing responses in immunized rodents than did a similarly conjugated proline-stabilized S-protein ectodomain. Nonetheless, the native RBD expresses inefficiently, limiting its usefulness as a vaccine antigen. However, we show that an RBD engineered with four novel glycosylation sites (gRBD) expresses markedly more efficiently, and generates a more potent neutralizing responses as a DNA vaccine antigen, than the wild-type RBD or the full-length S protein, especially when fused to multivalent carriers such as an H. pylori ferritin 24-mer. Further, gRBD is more immunogenic than the wild-type RBD when administered as a subunit protein vaccine. Our data suggest that multivalent gRBD antigens can reduce costs and doses, and improve the immunogenicity, of all major classes of SARS-CoV-2 vaccines.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":121025,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":559549,"name":"Wenhui He","orcid":"0000-0002-3176-1385","position":1,"is_corresponding":false},{"id":106930,"name":"Huihui Mou","orcid":null,"position":2,"is_corresponding":false},{"id":106928,"name":"Lizhou Zhang","orcid":"0000-0002-2637-9712","position":3,"is_corresponding":false},{"id":559550,"name":"Yan Guo","orcid":"0000-0002-7072-5344","position":4,"is_corresponding":false},{"id":559551,"name":"Jing Chang","orcid":"0000-0002-8973-6377","position":5,"is_corresponding":false},{"id":559552,"name":"Shoujiao Peng","orcid":"0000-0003-3086-8372","position":6,"is_corresponding":false},{"id":106931,"name":"Amrita Ojha","orcid":"0000-0001-9594-9195","position":7,"is_corresponding":false},{"id":559553,"name":"Rubens Tavora","orcid":"0000-0002-6392-7095","position":8,"is_corresponding":false},{"id":559554,"name":"Mark S. Parcells","orcid":"0000-0003-0311-3820","position":9,"is_corresponding":false},{"id":559555,"name":"Guangxiang Luo","orcid":"0000-0002-0354-6020","position":10,"is_corresponding":false},{"id":106938,"name":"Wenhui Li","orcid":"0000-0003-1305-7404","position":11,"is_corresponding":false},{"id":559556,"name":"Guocai Zhong","orcid":"0000-0002-7609-9575","position":12,"is_corresponding":false},{"id":106941,"name":"Hyeryun Choe","orcid":"0000-0003-4538-7176","position":13,"is_corresponding":false},{"id":104360,"name":"Michael Farzan","orcid":"0000-0002-2990-5319","position":14,"is_corresponding":false},{"id":106933,"name":"Brian D. Quinlan","orcid":"0000-0003-2719-731X","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:38.147936Z","pmid":"33236008","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":[]}