{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T01:16:38Z","timestamp":1784337398440,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012599","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000}}],"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research & Development Program of China","award":["2023YFC2606004"],"award-info":[{"award-number":["2023YFC2606004"]}]},{"name":"The Guangdong Basic and Applied Basic Research Foundation","award":["2022B1515020075"],"award-info":[{"award-number":["2022B1515020075"]}]},{"name":"National Key Research & Development Program of China","award":["2021YFA1201000, 2021YFC2302400"],"award-info":[{"award-number":["2021YFA1201000, 2021YFC2302400"]}]},{"DOI":"10.13039\/501100012236","name":"Beijing Institute of Technology Research Fund Program for Young Scholars","doi-asserted-by":"publisher","award":["XSQD-6120220072"],"award-info":[{"award-number":["XSQD-6120220072"]}],"id":[{"id":"10.13039\/501100012236","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170939"],"award-info":[{"award-number":["32170939"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Science and Technology Program key projects","award":["No.2021B1212030014"],"award-info":[{"award-number":["No.2021B1212030014"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Emerging and recurrent infectious diseases caused by coronaviruses remain a significant public health concern. Here, we present a targeted approach to elicit antibodies capable of neutralizing SARS-CoV-2 variants and other SARS-related coronaviruses. By introducing amino acid mutations at mutation-prone sites, we engineered glycosylation modifications to the Receptor Binding Domain (RBD) of SARS-CoV-2, thereby exposing more conserved, yet less accessible epitopes. We developed both messenger RNA (mRNA) and recombination subunit vaccines using these engineered-RBDs (M1, M2) and the wild-type RBD as immunogens. The engineered-RBD vaccines elicited robust neutralizing responses against various SARS-CoV-2 variants as well as SARS-CoV and WIV1-CoV, and conferred protection in mice challenged with the XBB.1.16 strain. Furthermore, We highlighted that glycan masking is a decisive factor in antibody binding changes and RBD-conserved antibody response. Additionally, the glycan-engineered RBD mRNA vaccines stimulated stronger cell-mediated immune responses. Our glycan modification strategy significantly enhances broad-spectrum neutralizing efficacy and cellular immunity, providing valuable insights for the development of vaccines against a wide range of SARS-related coronaviruses.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012599","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T17:48:09Z","timestamp":1727372889000},"page":"e1012599","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Development of Glycan-masked SARS-CoV-2 RBD vaccines against SARS-related coronaviruses"],"prefix":"10.1371","volume":"20","author":[{"given":"Zuxin","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoguo","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiping","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abid","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenguang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2196-2556","authenticated-orcid":true,"given":"Minghui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"issue":"9","key":"ppat.1012599.ref001","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/s41419-020-02995-9","article-title":"COVID19: an announced pandemic","volume":"11","author":"S Platto","year":"2020","journal-title":"Cell Death & Disease"},{"issue":"2","key":"ppat.1012599.ref002","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.cell.2022.12.018","article-title":"Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants","volume":"186","author":"Q Wang","year":"2023","journal-title":"Cell"},{"issue":"7","key":"ppat.1012599.ref003","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1056\/NEJMc2214314","article-title":"Substantial Neutralization Escape by SARS-CoV-2 Omicron Variants BQ.1.1 and XBB.1","volume":"388","author":"J Miller","year":"2023","journal-title":"The New England journal of medicine"},{"issue":"8","key":"ppat.1012599.ref004","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1002\/bit.27361","article-title":"Glycosylation as a tool for rational vaccine design","volume":"117","author":"V Hariharan","year":"2020","journal-title":"Biotechnol Bioeng"},{"key":"ppat.1012599.ref005","doi-asserted-by":"crossref","first-page":"1126034","DOI":"10.3389\/fimmu.2023.1126034","article-title":"Glycan masking in vaccine design: Targets, immunogens and applications","volume":"14","author":"CE Martina","year":"2023","journal-title":"Front Immunol"},{"issue":"12","key":"ppat.1012599.ref006","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20211003","article-title":"Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses","volume":"218","author":"R Shinnakasu","year":"2021","journal-title":"The Journal of experimental medicine"},{"issue":"639","key":"ppat.1012599.ref007","doi-asserted-by":"crossref","first-page":"eabm0899","DOI":"10.1126\/scitranslmed.abm0899","article-title":"Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models","volume":"14","author":"HY Huang","year":"2022","journal-title":"Sci Transl Med"},{"issue":"12","key":"ppat.1012599.ref008","doi-asserted-by":"crossref","first-page":"e1000571","DOI":"10.1371\/journal.pbio.1000571","article-title":"How can vaccines against influenza and other viral diseases be made more effective?","volume":"8","author":"PL Nara","year":"2010","journal-title":"PLoS Biol"},{"key":"ppat.1012599.ref009","doi-asserted-by":"crossref","first-page":"795741","DOI":"10.3389\/fimmu.2021.795741","article-title":"Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants","volume":"12","author":"WS Lin","year":"2021","journal-title":"Front Immunol"},{"issue":"1","key":"ppat.1012599.ref010","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1080\/22221751.2022.2056524","article-title":"A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates","volume":"11","author":"Y An","year":"2022","journal-title":"Emerg Microbes Infect"},{"issue":"7853","key":"ppat.1012599.ref011","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41586-021-03275-y","article-title":"BNT162b vaccines protect rhesus macaques from SARS-CoV-2","volume":"592","author":"AB Vogel","year":"2021","journal-title":"Nature"},{"issue":"10","key":"ppat.1012599.ref012","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/j.cell.2022.03.044","article-title":"Circular RNA vaccines against SARS-CoV-2 and emerging variants","volume":"185","author":"L Qu","year":"2022","journal-title":"Cell"},{"issue":"10","key":"ppat.1012599.ref013","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1038\/s41423-021-00752-2","article-title":"Neutralizing antibodies for the prevention and treatment of COVID-19","volume":"18","author":"L Du","year":"2021","journal-title":"Cell Mol Immunol"},{"issue":"3","key":"ppat.1012599.ref014","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/s41577-022-00784-3","article-title":"Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses","volume":"23","author":"Y Chen","year":"2023","journal-title":"Nature reviews Immunology"},{"issue":"7839","key":"ppat.1012599.ref015","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/s41586-020-2852-1","article-title":"SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies","volume":"588","author":"CO Barnes","year":"2020","journal-title":"Nature"},{"issue":"29","key":"ppat.1012599.ref016","doi-asserted-by":"crossref","first-page":"e2205784119","DOI":"10.1073\/pnas.2205784119","article-title":"A broad and potent neutralization epitope in SARS-related coronaviruses","volume":"119","author":"M Yuan","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7923","key":"ppat.1012599.ref017","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/s41586-022-04980-y","article-title":"BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection","volume":"608","author":"Y Cao","year":"2022","journal-title":"Nature"},{"key":"ppat.1012599.ref018","first-page":"109270","article-title":"An MPXV mRNA-LNP vaccine candidate elicits protective immune responses against monkeypox virus","author":"Y Tian","year":"2023","journal-title":"Chinese Chemical Letters"},{"issue":"6606","key":"ppat.1012599.ref019","first-page":"eabq0839","volume":"377","author":"AA Cohen","year":"2022","journal-title":"Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models"},{"issue":"1","key":"ppat.1012599.ref020","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41392-022-00950-y","article-title":"Advances in COVID-19 mRNA vaccine development","volume":"7","author":"E Fang","year":"2022","journal-title":"Signal transduction and targeted therapy"},{"issue":"10","key":"ppat.1012599.ref021","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1056\/NEJMe2111165","article-title":"Effectiveness of an Inactivated SARS-CoV-2 Vaccine","volume":"385","author":"A Wilder-Smith","year":"2021","journal-title":"The New England journal of medicine"},{"issue":"22","key":"ppat.1012599.ref022","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1056\/NEJMoa2202261","article-title":"Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults","volume":"386","author":"L Dai","year":"2022","journal-title":"The New England journal of medicine"},{"issue":"7","key":"ppat.1012599.ref023","doi-asserted-by":"crossref","first-page":"eabm1418","DOI":"10.1126\/sciadv.abm1418","article-title":"Thermostable ionizable lipid-like nanoparticle (iLAND) for RNAi treatment of hyperlipidemia","volume":"8","author":"B Hu","year":"2022","journal-title":"Sci Adv"},{"key":"ppat.1012599.ref024","doi-asserted-by":"crossref","first-page":"4277","DOI":"10.1038\/ncomms5277","article-title":"Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity","volume":"5","author":"KA Whitehead","year":"2014","journal-title":"Nature communications"},{"issue":"1","key":"ppat.1012599.ref025","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1038\/s41467-023-38435-3","article-title":"Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants","volume":"14","author":"T Tamura","year":"2023","journal-title":"Nature communications"},{"issue":"6","key":"ppat.1012599.ref026","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/s41565-022-01129-w","article-title":"Characterization of nanoparticles-based vaccines for COVID-19","volume":"17","author":"G Guerrini","year":"2022","journal-title":"Nat Nanotechnol"},{"key":"ppat.1012599.ref027","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.jconrel.2015.08.007","article-title":"Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes","volume":"217","author":"N Pardi","year":"2015","journal-title":"J Control Release"},{"issue":"3","key":"ppat.1012599.ref028","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.chom.2021.02.003","article-title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","volume":"29","author":"AJ Greaney","year":"2021","journal-title":"Cell Host Microbe"},{"issue":"4","key":"ppat.1012599.ref029","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.cell.2020.09.037","article-title":"Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology","volume":"183","author":"L Piccoli","year":"2020","journal-title":"Cell"},{"issue":"7815","key":"ppat.1012599.ref030","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41586-020-2349-y","article-title":"Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody","volume":"583","author":"D Pinto","year":"2020","journal-title":"Nature"},{"issue":"6","key":"ppat.1012599.ref031","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1016\/j.immuni.2020.10.023","article-title":"Cross-Neutralization of a SARS-CoV-2 Antibody to a Functionally Conserved Site Is Mediated by Avidity","volume":"53","author":"H Liu","year":"2020","journal-title":"Immunity"},{"issue":"2","key":"ppat.1012599.ref032","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1073\/pnas.1617174114","article-title":"Influenza A surface glycosylation and vaccine design","volume":"114","author":"CY Wu","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ppat.1012599.ref033","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41541-023-00635-9","article-title":"Hepatitis C virus E1 and modified E2 delivered from an mRNA vaccine induces protective immunity","volume":"8","author":"T Patra","year":"2023","journal-title":"NPJ vaccines"},{"key":"ppat.1012599.ref034","doi-asserted-by":"crossref","first-page":"110108","DOI":"10.1016\/j.vetmic.2024.110108","article-title":"Dual N-linked glycosylation at residues 133 and 158 in the hemagglutinin are essential for the efficacy of H7N9 avian influenza virus like particle vaccine in chickens and mice","volume":"294","author":"Y Wang","year":"2024","journal-title":"Veterinary microbiology"},{"issue":"1","key":"ppat.1012599.ref035","doi-asserted-by":"crossref","first-page":"6463","DOI":"10.1038\/s41467-024-50752-9","article-title":"Atavistic strategy for the treatment of hyperuricemia via ionizable liposomal mRNA","volume":"15","author":"M Zhang","year":"2024","journal-title":"Nature communications"},{"issue":"9","key":"ppat.1012599.ref036","doi-asserted-by":"crossref","first-page":"4634","DOI":"10.1128\/JVI.76.9.4634-4642.2002","article-title":"Highly stable trimers formed by human immunodeficiency virus type 1 envelope glycoproteins fused with the trimeric motif of T4 bacteriophage fibritin","volume":"76","author":"X Yang","year":"2002","journal-title":"J Virol"},{"issue":"5","key":"ppat.1012599.ref037","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.cell.2020.07.024","article-title":"A Thermostable mRNA Vaccine against COVID-19","volume":"182","author":"NN Zhang","year":"2020","journal-title":"Cell"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1012599","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012599","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T17:30:36Z","timestamp":1728408636000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012599"}},"subtitle":[],"editor":[{"given":"Haitao","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,9,26]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1012599","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1012599","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,26]]}}}