{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T22:54:59Z","timestamp":1776293699955,"version":"3.50.1"},"reference-count":26,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T00:00:00Z","timestamp":1613865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Science and Technology Planning Project of Shenzhen City","award":["JSGG20200225152008136, 20190804095916056"],"award-info":[{"award-number":["JSGG20200225152008136, 20190804095916056"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971927"],"award-info":[{"award-number":["81971927"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>With the rapid global spread of the Coronavirus Disease 2019 (COVID-19) pandemic, a safe and effective vaccine against human coronaviruses (HCoVs) is believed to be a top priority in the field of public health. Due to the frequent outbreaks of different HCoVs, the development of a pan-HCoVs vaccine is of great value to biomedical science. The antigen design is a key prerequisite for vaccine efficacy, and we therefore developed a novel antigen with broad coverage based on the genetic algorithm of mosaic strategy. The designed antigen has a potentially broad coverage of conserved cytotoxic T lymphocyte (CTL) epitopes to the greatest extent, including the existing epitopes from all reported HCoV sequences (HCoV-NL63, HCoV-229E, HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2). This novel antigen is expected to induce strong CTL responses with broad coverage by targeting conserved epitopes against multiple coronaviruses.<\/jats:p>","DOI":"10.3390\/v13020333","type":"journal-article","created":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T23:59:31Z","timestamp":1613951971000},"page":"333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Rational Design of a Pan-Coronavirus Vaccine Based on Conserved CTL Epitopes"],"prefix":"10.3390","volume":"13","author":[{"given":"Minchao","family":"Li","sequence":"first","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 514400, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinfeng","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 514400, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiting","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 514400, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyu","family":"Wen","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 514400, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhui","family":"Cai","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. 333 Lakeside Dr, Foster City, CA 94404, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5952-3813","authenticated-orcid":false,"given":"Jeffrey","family":"Wallin","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. 333 Lakeside Dr, Foster City, CA 94404, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuelong","family":"Shu","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 514400, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8184-8430","authenticated-orcid":false,"given":"Xiangjun","family":"Du","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 514400, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2000-7053","authenticated-orcid":false,"given":"Caijun","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 514400, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,21]]},"reference":[{"key":"ref_1","unstructured":"Chinese Center for Disease Control and Prevention (2021, February 07). Distribution of COVID-19. Available online: http:\/\/2019ncov.chinacdc.cn\/2019-nCoV\/global.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1002\/jmv.25681","article-title":"Emerging coronaviruses: Genome structure, replication, and pathogenesis","volume":"92","author":"Chen","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3201\/eid2602.190697","article-title":"Middle East Respiratory Syndrome Coronavirus Transmission","volume":"26","author":"Killerby","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.4049\/jimmunol.1700893","article-title":"NetMHCpan-4.0: Improved Peptide-MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data","volume":"199","author":"Jurtz","year":"2017","journal-title":"J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/ng.3576","article-title":"Deep sequencing of the MHC region in the Chinese population contributes to studies of complex disease","volume":"48","author":"Zhou","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1034\/j.1399-0039.2003.00062.x","article-title":"New allele frequency database: http:\/\/www.allelefrequencies.net","volume":"61","author":"Middleton","year":"2003","journal-title":"Tissue Antigens"},{"key":"ref_7","first-page":"783","article-title":"Allele frequency net database (AFND) 2020 update: Gold-standard data classification, open access genotype data and new query tools","volume":"48","author":"McCabe","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1093\/bioinformatics\/bts565","article-title":"CD-HIT: Accelerated for clustering the next generation sequencing data","volume":"28","author":"Limin","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.chom.2020.03.002","article-title":"Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2","volume":"27","author":"Grifoni","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nm1461","article-title":"Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants","volume":"13","author":"Fischer","year":"2007","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.cell.2013.09.061","article-title":"Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys","volume":"155","author":"Barouch","year":"2013","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13300","DOI":"10.1128\/JVI.01532-14","article-title":"Broad protection against avian influenza virus by using a modified vacciniaAnkara virus expressing a mosaic hemagglutinin gene","volume":"88","author":"Kamlangdee","year":"2014","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1126\/science.abc1932","article-title":"Rapid development of an inactivated vaccine candidate for SARS-CoV-2","volume":"369","author":"Gao","year":"2020","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/S0140-6736(16)32617-4","article-title":"Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: A single-centre, randomised, double-blind, placebo-controlled, phase 2 trial","volume":"389","author":"Zhu","year":"2017","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1016\/j.vaccine.2014.04.016","article-title":"Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice","volume":"32","author":"Coleman","year":"2014","journal-title":"Vaccine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12672","DOI":"10.1128\/JVI.78.22.12672-12676.2004","article-title":"Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets","volume":"78","author":"Weingartl","year":"2004","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e123158","DOI":"10.1172\/jci.insight.123158","article-title":"Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection","volume":"4","author":"Liu","year":"2019","journal-title":"JCI Insight"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1016\/j.vaccine.2016.02.063","article-title":"Memory T cell responses targeting the SARS coronavirus persist up to 11 yearspost-infection","volume":"34","author":"Ng","year":"2016","journal-title":"Vaccine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/j.immuni.2016.05.006","article-title":"Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses","volume":"44","author":"Zhao","year":"2016","journal-title":"Immunity"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/s41586-020-2550-z","article-title":"SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls","volume":"584","author":"Tan","year":"2020","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/j.cell.2020.05.015","article-title":"Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals","volume":"181","author":"Grifoni","year":"2020","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1038\/s41590-020-0782-6","article-title":"Broad and strong memory CD4(+) and CD8(+) T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19","volume":"21","author":"Peng","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13073-020-00767-w","article-title":"Sequence-based prediction of SARS-CoV-2 vaccine targets using a mass spectrometry-based bioinformatics predictor identifies immunogenic T cell epitopes","volume":"12","author":"Poran","year":"2020","journal-title":"Genome Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1126\/science.abd3871","article-title":"Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans","volume":"370","author":"Mateus","year":"2020","journal-title":"Science"},{"key":"ref_25","first-page":"4389089","article-title":"SARS-CoV-2 Envelope and Membrane Proteins: Structural Differences Linked to Virus Characteristics?","volume":"2020","author":"Martina","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12985-019-1182-0","article-title":"Coronavirus envelope protein: Current knowledge","volume":"16","author":"Schoeman","year":"2019","journal-title":"Virol. J."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/2\/333\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:27:27Z","timestamp":1760160447000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/2\/333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,21]]},"references-count":26,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["v13020333"],"URL":"https:\/\/doi.org\/10.3390\/v13020333","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,21]]}}}