{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:11:04Z","timestamp":1789639864303,"version":"4.0.0"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T00:00:00Z","timestamp":1598313600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T00:00:00Z","timestamp":1598313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across the globe, infecting millions of people and generating societal disruption on a level not seen since the 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth knowledge on betacoronavirus immunology. To that end, we developed a computational workflow using a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41\u00a0T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen. To our knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for vaccine development.<\/jats:p>","DOI":"10.1038\/s41598-020-70864-8","type":"journal-article","created":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T06:04:04Z","timestamp":1598335444000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome"],"prefix":"10.1038","volume":"10","author":[{"given":"Stephen N.","family":"Crooke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna G.","family":"Ovsyannikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Poland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,25]]},"reference":[{"key":"70864_CR1","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","volume":"579","author":"F Wu","year":"2020","unstructured":"Wu, F. et al. A new coronavirus associated with human respiratory disease in China. Nature 579, 265\u2013269. https:\/\/doi.org\/10.1038\/s41586-020-2008-3 (2020).","journal-title":"Nature"},{"key":"70864_CR2","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/S0140-6736(20)30154-9","volume":"395","author":"JF Chan","year":"2020","unstructured":"Chan, J. F. et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 395, 514\u2013523. https:\/\/doi.org\/10.1016\/S0140-6736(20)30154-9 (2020).","journal-title":"Lancet"},{"key":"70864_CR3","doi-asserted-by":"publisher","first-page":"157","DOI":"10.23750\/abm.v91i1.9397","volume":"91","author":"D Cucinotta","year":"2020","unstructured":"Cucinotta, D. & Vanelli, M. WHO declares COVID-19 a pandemic. Acta Biomed. 91, 157\u2013160. https:\/\/doi.org\/10.23750\/abm.v91i1.9397 (2020).","journal-title":"Acta Biomed."},{"key":"70864_CR4","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/S0140-6736(20)30211-7","volume":"395","author":"N Chen","year":"2020","unstructured":"Chen, N. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 395, 507\u2013513. https:\/\/doi.org\/10.1016\/S0140-6736(20)30211-7 (2020).","journal-title":"Lancet"},{"key":"70864_CR5","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1001\/jama.2020.1585","volume":"323","author":"D Wang","year":"2020","unstructured":"Wang, D. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 323, 1061\u20131069. https:\/\/doi.org\/10.1001\/jama.2020.1585 (2020).","journal-title":"JAMA"},{"key":"70864_CR6","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","volume":"395","author":"C Huang","year":"2020","unstructured":"Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497\u2013506. https:\/\/doi.org\/10.1016\/S0140-6736(20)30183-5 (2020).","journal-title":"Lancet"},{"key":"70864_CR7","unstructured":"World Health Organization. Coronavirus disease (COVID-19) Situation Report - 113. https:\/\/www.who.int\/docs\/default-source\/coronaviruse\/situation-reports\/20200512-covid-19-sitrep-113.pdf?sfvrsn=feac3b6d_2. (2020)."},{"key":"70864_CR8","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1056\/NEJMoa030747","volume":"348","author":"C Drosten","year":"2003","unstructured":"Drosten, C. et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 348, 1967\u20131976. https:\/\/doi.org\/10.1056\/NEJMoa030747 (2003).","journal-title":"N. Engl. J. Med."},{"key":"70864_CR9","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1056\/NEJMoa030781","volume":"348","author":"TG Ksiazek","year":"2003","unstructured":"Ksiazek, T. G. et al. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 348, 1953\u20131966. https:\/\/doi.org\/10.1056\/NEJMoa030781 (2003).","journal-title":"N. Engl. J. Med."},{"key":"70864_CR10","doi-asserted-by":"publisher","first-page":"1814","DOI":"10.1056\/NEJMoa1211721","volume":"367","author":"AM Zaki","year":"2012","unstructured":"Zaki, A. M., van Boheemen, S., Bestebroer, T. M., Osterhaus, A. D. & Fouchier, R. A. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 367, 1814\u20131820. https:\/\/doi.org\/10.1056\/NEJMoa1211721 (2012).","journal-title":"N. Engl. J. Med."},{"key":"70864_CR11","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1126\/science.1118391","volume":"310","author":"W Li","year":"2005","unstructured":"Li, W. et al. Bats are natural reservoirs of SARS-like coronaviruses. Science 310, 676\u2013679. https:\/\/doi.org\/10.1126\/science.1118391 (2005).","journal-title":"Science"},{"key":"70864_CR12","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","volume":"579","author":"P Zhou","year":"2020","unstructured":"Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270\u2013273. https:\/\/doi.org\/10.1038\/s41586-020-2012-7 (2020).","journal-title":"Nature"},{"key":"70864_CR13","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.3201\/eid1911.131172","volume":"19","author":"ZA Memish","year":"2013","unstructured":"Memish, Z. A. et al. Middle East respiratory syndrome coronavirus in bats, Saudi Arabia. Emerg. Infect. Dis. 19, 1819\u20131823. https:\/\/doi.org\/10.3201\/eid1911.131172 (2013).","journal-title":"Emerg. Infect. Dis."},{"key":"70864_CR14","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/S1473-3099(13)70690-X","volume":"14","author":"BL Haagmans","year":"2014","unstructured":"Haagmans, B. L. et al. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis. 14, 140\u2013145. https:\/\/doi.org\/10.1016\/S1473-3099(13)70690-X (2014).","journal-title":"Lancet Infect Dis."},{"key":"70864_CR15","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","volume":"181","author":"AC Walls","year":"2020","unstructured":"Walls, A. C. et al. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 181, 281\u2013292. https:\/\/doi.org\/10.1016\/j.cell.2020.02.058 (2020).","journal-title":"Cell"},{"key":"70864_CR16","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00203-20","author":"S Weston","year":"2020","unstructured":"Weston, S. & Frieman, M. B. COVID-19: knowns, unknowns, and questions. mSphere. https:\/\/doi.org\/10.1128\/mSphere.00203-20 (2020).","journal-title":"mSphere."},{"key":"70864_CR17","unstructured":"World Health Organization. Draft landscape of COVID-19 candidate vaccines. https:\/\/www.who.int\/who-documents-detail\/draft-landscape-of-covid-19-candidate-vaccines. (2020)."},{"key":"70864_CR18","doi-asserted-by":"publisher","first-page":"4219","DOI":"10.1016\/j.vaccine.2020.04.073","volume":"38","author":"GA Poland","year":"2020","unstructured":"Poland, G. A. Tortoises, hares, and vaccines: a cautionary note for SARS-CoV-2 vaccine development. Vaccine 38, 4219\u20134220 (2020).","journal-title":"Vaccine"},{"key":"70864_CR19","doi-asserted-by":"publisher","first-page":"e35421","DOI":"10.1371\/journal.pone.0035421","volume":"7","author":"CT Tseng","year":"2012","unstructured":"Tseng, C. T. et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS ONE 7, e35421. https:\/\/doi.org\/10.1371\/journal.pone.0035421 (2012).","journal-title":"PLoS ONE"},{"key":"70864_CR20","doi-asserted-by":"publisher","first-page":"e525","DOI":"10.1371\/journal.pmed.0030525","volume":"3","author":"D Deming","year":"2006","unstructured":"Deming, D. et al. Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants. PLoS Med. 3, e525. https:\/\/doi.org\/10.1371\/journal.pmed.0030525 (2006).","journal-title":"PLoS Med."},{"key":"70864_CR21","doi-asserted-by":"publisher","first-page":"6337","DOI":"10.4049\/jimmunol.181.9.6337","volume":"181","author":"F Yasui","year":"2008","unstructured":"Yasui, F. et al. Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV. J Immunol. 181, 6337\u20136348. https:\/\/doi.org\/10.4049\/jimmunol.181.9.6337 (2008).","journal-title":"J Immunol."},{"key":"70864_CR22","doi-asserted-by":"publisher","first-page":"12201","DOI":"10.1128\/JVI.06048-11","volume":"85","author":"M Bolles","year":"2011","unstructured":"Bolles, M. et al. A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge. J Virol. 85, 12201\u201312215. https:\/\/doi.org\/10.1128\/JVI.06048-11 (2011).","journal-title":"J Virol."},{"key":"70864_CR23","doi-asserted-by":"publisher","first-page":"12672","DOI":"10.1128\/JVI.78.22.12672-12676.2004","volume":"78","author":"H Weingartl","year":"2004","unstructured":"Weingartl, H. et al. Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J Virol. 78, 12672\u201312676. https:\/\/doi.org\/10.1128\/JVI.78.22.12672-12676.2004 (2004).","journal-title":"J Virol."},{"key":"70864_CR24","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/S0140-6736(20)30251-8","volume":"395","author":"R Lu","year":"2020","unstructured":"Lu, R. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395, 565\u2013574. https:\/\/doi.org\/10.1016\/S0140-6736(20)30251-8 (2020).","journal-title":"Lancet"},{"key":"70864_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.015","author":"A Grifoni","year":"2020","unstructured":"Grifoni, A. et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell https:\/\/doi.org\/10.1016\/j.cell.2020.05.015 (2020).","journal-title":"Cell"},{"key":"70864_CR26","doi-asserted-by":"publisher","unstructured":"Braun, J. et al. Presence of SARS-CoV-2 reactive T cells in COVID-19 patients and healthy donors. Preprint at https:\/\/doi.org\/10.1101\/2020.04.17.20061440 (2020).","DOI":"10.1101\/2020.04.17.20061440"},{"key":"70864_CR27","doi-asserted-by":"publisher","unstructured":"Peng, Y. et al. Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients. Preprint at https:\/\/doi.org\/10.1101\/2020.06.05.134551 (2020).","DOI":"10.1101\/2020.06.05.134551"},{"key":"70864_CR28","doi-asserted-by":"publisher","first-page":"11034","DOI":"10.1128\/JVI.01505-14","volume":"88","author":"R Channappanavar","year":"2014","unstructured":"Channappanavar, R., Fett, C., Zhao, J., Meyerholz, D. K. & Perlman, S. Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection. J Virol. 88, 11034\u201311044. https:\/\/doi.org\/10.1128\/JVI.01505-14 (2014).","journal-title":"J Virol."},{"key":"70864_CR29","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1016\/j.vaccine.2016.02.063","volume":"34","author":"OW Ng","year":"2016","unstructured":"Ng, O. W. et al. Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection. Vaccine 34, 2008\u20132014. https:\/\/doi.org\/10.1016\/j.vaccine.2016.02.063 (2016).","journal-title":"Vaccine"},{"key":"70864_CR30","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1016\/j.immuni.2016.05.006","volume":"44","author":"J Zhao","year":"2016","unstructured":"Zhao, J. et al. Airway memory CD4(+) T cells mediate protective immunity against emerging respiratory coronaviruses. Immunity 44, 1379\u20131391. https:\/\/doi.org\/10.1016\/j.immuni.2016.05.006 (2016).","journal-title":"Immunity"},{"key":"70864_CR31","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1074\/mcp.M115.057356","volume":"15","author":"E Lorente","year":"2016","unstructured":"Lorente, E. et al. Structural and nonstructural viral proteins are targets of T-helper immune response against human respiratory syncytial virus. Mol. Cell Proteomics 15, 2141\u20132151. https:\/\/doi.org\/10.1074\/mcp.M115.057356 (2016).","journal-title":"Mol. Cell Proteomics"},{"key":"70864_CR32","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1038\/mt.2013.287","volume":"22","author":"PP Ip","year":"2014","unstructured":"Ip, P. P. et al. Alphavirus-based vaccines encoding nonstructural proteins of hepatitis C virus induce robust and protective T-cell responses. Mol. Ther. 22, 881\u2013890. https:\/\/doi.org\/10.1038\/mt.2013.287 (2014).","journal-title":"Mol. Ther."},{"key":"70864_CR33","doi-asserted-by":"publisher","first-page":"e2330","DOI":"10.1371\/journal.pntd.0002330","volume":"7","author":"HR Henriques","year":"2013","unstructured":"Henriques, H. R. et al. Targeting the non-structural protein 1 from dengue virus to a dendritic cell population confers protective immunity to lethal virus challenge. PLoS Negl. Trop. Dis. 7, e2330. https:\/\/doi.org\/10.1371\/journal.pntd.0002330 (2013).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"70864_CR34","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/978-1-4939-1115-8_3","volume":"1184","author":"N Tomar","year":"2014","unstructured":"Tomar, N. & De, R. K. Immunoinformatics: a brief review. Methods Mol. Biol. 1184, 23\u201355. https:\/\/doi.org\/10.1007\/978-1-4939-1115-8_3 (2014).","journal-title":"Methods Mol. Biol."},{"key":"70864_CR35","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s13073-015-0245-0","volume":"7","author":"L Backert","year":"2015","unstructured":"Backert, L. & Kohlbacher, O. Immunoinformatics and epitope prediction in the age of genomic medicine. Genome Med. 7, 119. https:\/\/doi.org\/10.1186\/s13073-015-0245-0 (2015).","journal-title":"Genome Med."},{"key":"70864_CR36","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/imm.12889","volume":"154","author":"KK Jensen","year":"2018","unstructured":"Jensen, K. K. et al. Improved methods for predicting peptide binding affinity to MHC class II molecules. Immunology 154, 394\u2013406. https:\/\/doi.org\/10.1111\/imm.12889 (2018).","journal-title":"Immunology"},{"key":"70864_CR37","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1186\/s12967-019-2116-8","volume":"17","author":"M Tahir Ul Qamar","year":"2019","unstructured":"Tahir Ul Qamar, M. et al. Epitope-based peptide vaccine design and target site depiction against Middle East Respiratory Syndrome Coronavirus: an immune-informatics study. J Transl Med. 17, 362. https:\/\/doi.org\/10.1186\/s12967-019-2116-8 (2019).","journal-title":"J Transl Med."},{"key":"70864_CR38","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.chom.2020.03.002","volume":"27","author":"A Grifoni","year":"2020","unstructured":"Grifoni, A. et al. A Sequence homology and bioinformatic approach can predict candidate targets for immune responses to SARS-CoV-2. Cell Host Microbe 27, 671-680 e672. https:\/\/doi.org\/10.1016\/j.chom.2020.03.002 (2020).","journal-title":"Cell Host Microbe"},{"key":"70864_CR39","doi-asserted-by":"publisher","unstructured":"Fast, E., Altman, R. B. & Chen, B. Potential T-cell and B-cell Epitopes of 2019-nCoV. Preprint at https:\/\/doi.org\/10.1101\/2020.02.19.955484 (2020).","DOI":"10.1101\/2020.02.19.955484"},{"key":"70864_CR40","unstructured":"Seema, M. T cell epitope-based vaccine design for pandemic novel coronavirus 2019-nCoV. Preprint at https:\/\/chemrxiv.org\/articles\/T_Cell_Epitope-Based_Vaccine_Design_for_Pandemic_Novel_Coronavirus_2019-nCoV\/12029523 (2020)."},{"key":"70864_CR41","doi-asserted-by":"publisher","unstructured":"Feng, Y.-E. et al. Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus in China (SARS-CoV-2). Preprint at 2020, https:\/\/doi.org\/10.1101\/2020.03.03.962332 (2019).","DOI":"10.1101\/2020.03.03.962332"},{"key":"70864_CR42","doi-asserted-by":"publisher","first-page":"W636","DOI":"10.1093\/nar\/gkz268","volume":"47","author":"F Madeira","year":"2019","unstructured":"Madeira, F. et al. The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucl. Acids Res. 47, W636\u2013W641. https:\/\/doi.org\/10.1093\/nar\/gkz268 (2019).","journal-title":"Nucl. Acids Res."},{"key":"70864_CR43","doi-asserted-by":"publisher","unstructured":"Srivastava, S. et al. Structural basis to design multi-epitope vaccines against Novel Coronavirus 19 (COVID19) infection, the ongoing pandemic emergency: an in silico approach. Preprint at https:\/\/doi.org\/10.1101\/2020.04.01.019299 (2020).","DOI":"10.1101\/2020.04.01.019299"},{"key":"70864_CR44","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1186\/1471-2105-8-424","volume":"8","author":"MV Larsen","year":"2007","unstructured":"Larsen, M. V. et al. Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction. BMC Bioinform. 8, 424 (2007).","journal-title":"BMC Bioinform."},{"key":"70864_CR45","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1002\/eji.200425811","volume":"35","author":"MV Larsen","year":"2005","unstructured":"Larsen, M. V. et al. An integrative approach to CTL epitope prediction: a combined algorithm integrating MHC class I binding, TAP transport efficiency, and proteasomal cleavage predictions. Eur. J. Immunol. 35, 2295\u20132303. https:\/\/doi.org\/10.1002\/eji.200425811 (2005).","journal-title":"Eur. J. Immunol."},{"key":"70864_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00251-008-0341-z","volume":"61","author":"I Hoof","year":"2009","unstructured":"Hoof, I. et al. NetMHCpan, a method for MHC class I binding prediction beyond humans. Immunogenetics 61, 1\u201313. https:\/\/doi.org\/10.1007\/s00251-008-0341-z (2009).","journal-title":"Immunogenetics"},{"key":"70864_CR47","doi-asserted-by":"publisher","first-page":"3360","DOI":"10.4049\/jimmunol.1700893","volume":"199","author":"V Jurtz","year":"2017","unstructured":"Jurtz, V. et al. NetMHCpan-4.0: Improved peptide-MHC class I interaction predictions integrating eluted ligand and peptide binding affinity data. J. Immunol. 199, 3360\u20133368. https:\/\/doi.org\/10.4049\/jimmunol.1700893 (2017).","journal-title":"J. Immunol."},{"key":"70864_CR48","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s13073-016-0288-x","volume":"8","author":"M Nielsen","year":"2016","unstructured":"Nielsen, M. & Andreatta, M. NetMHCpan-3.0; improved prediction of binding to MHC class I molecules integrating information from multiple receptor and peptide length datasets. Genome Med. 8, 33. https:\/\/doi.org\/10.1186\/s13073-016-0288-x (2016).","journal-title":"Genome Med."},{"key":"70864_CR49","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s00251-011-0513-0","volume":"63","author":"J Greenbaum","year":"2011","unstructured":"Greenbaum, J. et al. Functional classification of class II human leukocyte antigen (HLA) molecules reveals seven different supertypes and a surprising degree of repertoire sharing across supertypes. Immunogenetics 63, 325\u2013335 (2011).","journal-title":"Immunogenetics"},{"key":"70864_CR50","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1471-2105-8-4","volume":"8","author":"IA Doytchinova","year":"2007","unstructured":"Doytchinova, I. A. & Flower, D. R. VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinform. 8, 4. https:\/\/doi.org\/10.1186\/1471-2105-8-4 (2007).","journal-title":"BMC Bioinform."},{"key":"70864_CR51","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1016\/j.vaccine.2006.09.032","volume":"25","author":"IA Doytchinova","year":"2007","unstructured":"Doytchinova, I. A. & Flower, D. R. Identifying candidate subunit vaccines using an alignment-independent method based on principal amino acid properties. Vaccine 25, 856\u2013866. https:\/\/doi.org\/10.1016\/j.vaccine.2006.09.032 (2007).","journal-title":"Vaccine"},{"key":"70864_CR52","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/1471-2105-7-153","volume":"7","author":"HH Bui","year":"2006","unstructured":"Bui, H. H. et al. Predicting population coverage of T-cell epitope-based diagnostics and vaccines. BMC Bioinform. 7, 153 (2006).","journal-title":"BMC Bioinform."},{"key":"70864_CR53","doi-asserted-by":"publisher","first-page":"e73957","DOI":"10.1371\/journal.pone.0073957","volume":"8","author":"S Gupta","year":"2013","unstructured":"Gupta, S. et al. In silico approach for predicting toxicity of peptides and proteins. PLoS ONE 8, e73957. https:\/\/doi.org\/10.1371\/journal.pone.0073957 (2013).","journal-title":"PLoS ONE"},{"key":"70864_CR54","doi-asserted-by":"publisher","first-page":"3020","DOI":"10.1093\/bioinformatics\/btz029","volume":"35","author":"S Maurer-Stroh","year":"2019","unstructured":"Maurer-Stroh, S. et al. AllerCatPro-prediction of protein allergenicity potential from the protein sequence. Bioinformatics 35, 3020\u20133027. https:\/\/doi.org\/10.1093\/bioinformatics\/btz029 (2019).","journal-title":"Bioinformatics"},{"key":"70864_CR55","doi-asserted-by":"publisher","first-page":"W294","DOI":"10.1093\/nar\/gks493","volume":"40","author":"J Ko","year":"2012","unstructured":"Ko, J., Park, H., Heo, L. & Seok, C. GalaxyWEB server for protein structure prediction and refinement. Nucl. Acids Res. 40, W294-297. https:\/\/doi.org\/10.1093\/nar\/gks493 (2012).","journal-title":"Nucl. Acids Res."},{"key":"70864_CR56","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1107\/S1744309108012396","volume":"64","author":"G Roder","year":"2008","unstructured":"Roder, G., Kristensen, O., Kastrup, J. S., Buus, S. & Gajhede, M. Structure of a SARS coronavirus-derived peptide bound to the human major histocompatibility complex class I molecule HLA-B*1501. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64, 459\u2013462. https:\/\/doi.org\/10.1107\/S1744309108012396 (2008).","journal-title":"Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun."},{"key":"70864_CR57","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen, E. F. et al. UCSF Chimera\u2013a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605\u20131612. https:\/\/doi.org\/10.1002\/jcc.20084 (2004).","journal-title":"J. Comput. Chem."},{"key":"70864_CR58","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1745-7580-2-2","volume":"2","author":"JE Larsen","year":"2006","unstructured":"Larsen, J. E., Lund, O. & Nielsen, M. Improved method for predicting linear B-cell epitopes. Immunome Res. 2, 2. https:\/\/doi.org\/10.1186\/1745-7580-2-2 (2006).","journal-title":"Immunome Res."},{"key":"70864_CR59","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1126\/science.abb2507","volume":"367","author":"D Wrapp","year":"2020","unstructured":"Wrapp, D. et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367, 1260\u20131263. https:\/\/doi.org\/10.1126\/science.abb2507 (2020).","journal-title":"Science"},{"key":"70864_CR60","doi-asserted-by":"publisher","first-page":"2558","DOI":"10.1110\/ps.062405906","volume":"15","author":"P Haste Andersen","year":"2006","unstructured":"Haste Andersen, P., Nielsen, M. & Lund, O. Prediction of residues in discontinuous B-cell epitopes using protein 3D structures. Protein Sci. 15, 2558\u20132567. https:\/\/doi.org\/10.1110\/ps.062405906 (2006).","journal-title":"Protein Sci."},{"key":"70864_CR61","doi-asserted-by":"crossref","first-page":"5586","DOI":"10.4049\/jimmunol.153.12.5586","volume":"153","author":"A Sette","year":"1994","unstructured":"Sette, A. et al. The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J. Immunol. 153, 5586\u20135592 (1994).","journal-title":"J. Immunol."},{"key":"70864_CR62","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1107\/S0907444906027636","volume":"62","author":"G Roder","year":"2006","unstructured":"Roder, G. et al. Crystal structures of two peptide-HLA-B*1501 complexes; structural characterization of the HLA-B62 supertype. Acta Crystallogr. D Biol. Crystallogr. 62, 1300\u20131310. https:\/\/doi.org\/10.1107\/S0907444906027636 (2006).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"70864_CR63","doi-asserted-by":"publisher","unstructured":"Okba, N. M. A. et al. SARS-CoV-2 specific antibody responses in COVID-19 patients. Preprint at https:\/\/doi.org\/10.1101\/2020.03.18.20038059 (2020).","DOI":"10.1101\/2020.03.18.20038059"},{"key":"70864_CR64","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1021\/acsinfecdis.6b00006","volume":"2","author":"Q Wang","year":"2016","unstructured":"Wang, Q. et al. Immunodominant SARS coronavirus epitopes in humans elicited both enhancing and neutralizing effects on infection in non-human primates. ACS Infect. Dis. 2, 361\u2013376. https:\/\/doi.org\/10.1021\/acsinfecdis.6b00006 (2016).","journal-title":"ACS Infect. Dis."},{"key":"70864_CR65","doi-asserted-by":"publisher","first-page":"6536","DOI":"10.18632\/aging.103102","volume":"12","author":"L Zhang","year":"2020","unstructured":"Zhang, L. et al. Anti-SARS-CoV-2 virus antibody levels in convalescent plasma of six donors who have recovered from COVID-19. Aging 12, 6536\u20136542. https:\/\/doi.org\/10.18632\/aging.103102 (2020).","journal-title":"Aging"},{"key":"70864_CR66","doi-asserted-by":"publisher","first-page":"e1006271","DOI":"10.1371\/journal.ppat.1006271","volume":"13","author":"MB Doud","year":"2017","unstructured":"Doud, M. B., Hensley, S. E. & Bloom, J. D. Complete mapping of viral escape from neutralizing antibodies. PLoS Pathog. 13, e1006271. https:\/\/doi.org\/10.1371\/journal.ppat.1006271 (2017).","journal-title":"PLoS Pathog."},{"key":"70864_CR67","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.3389\/fimmu.2018.01194","volume":"9","author":"ML Keck","year":"2018","unstructured":"Keck, M. L., Wrensch, F., Pierce, B. G., Baumert, T. F. & Foung, S. K. H. Mapping determinants of virus neutralization and viral escape for rational design of a hepatitis C virus vaccine. Front. Immunol. 9, 1194. https:\/\/doi.org\/10.3389\/fimmu.2018.01194 (2018).","journal-title":"Front. Immunol."},{"key":"70864_CR68","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/S0198-8859(99)00155-X","volume":"61","author":"JM Ellis","year":"2000","unstructured":"Ellis, J. M. et al. Frequencies of HLA-A2 alleles in five U.S. population groups. Predominance of A*02011 and identification of HLA-A*0231. Human Immunol. 61, 334\u2013340 (2000).","journal-title":"Human Immunol."},{"key":"70864_CR69","doi-asserted-by":"publisher","unstructured":"Nguyen, A. et al. Human leukocyte antigen susceptibility map for SARS-CoV-2. Preprint at https:\/\/doi.org\/10.1101\/2020.03.22.20040600 (2020).","DOI":"10.1101\/2020.03.22.20040600"},{"key":"70864_CR70","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1002\/jmv.20096","volume":"73","author":"LR Huang","year":"2004","unstructured":"Huang, L. R. et al. Evaluation of antibody responses against SARS coronaviral nucleocapsid or spike proteins by immunoblotting or ELISA. J Med Virol. 73, 338\u2013346. https:\/\/doi.org\/10.1002\/jmv.20096 (2004).","journal-title":"J Med Virol."},{"key":"70864_CR71","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1016\/j.micinf.2005.02.006","volume":"7","author":"M Qiu","year":"2005","unstructured":"Qiu, M. et al. Antibody responses to individual proteins of SARS coronavirus and their neutralization activities. Microbes Infect. 7, 882\u2013889. https:\/\/doi.org\/10.1016\/j.micinf.2005.02.006 (2005).","journal-title":"Microbes Infect."},{"key":"70864_CR72","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/s41423-020-0400-4","volume":"17","author":"W Tai","year":"2020","unstructured":"Tai, W. et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol. Immunol. 17, 613\u2013620 (2020).","journal-title":"Cell Mol. Immunol."},{"key":"70864_CR73","doi-asserted-by":"publisher","first-page":"5612","DOI":"10.1016\/j.febslet.2006.08.085","volume":"580","author":"F Zeng","year":"2006","unstructured":"Zeng, F. et al. Quantitative comparison of the efficiency of antibodies against S1 and S2 subunit of SARS coronavirus spike protein in virus neutralization and blocking of receptor binding: implications for the functional roles of S2 subunit. FEBS Lett. 580, 5612\u20135620. https:\/\/doi.org\/10.1016\/j.febslet.2006.08.085 (2006).","journal-title":"FEBS Lett."},{"key":"70864_CR74","doi-asserted-by":"publisher","first-page":"53","DOI":"10.4161\/mabs.2.1.10788","volume":"2","author":"JD Berry","year":"2010","unstructured":"Berry, J. D. et al. Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology. MAbs 2, 53\u201366. https:\/\/doi.org\/10.4161\/mabs.2.1.10788 (2010).","journal-title":"MAbs"},{"key":"70864_CR75","doi-asserted-by":"publisher","first-page":"5498","DOI":"10.1016\/j.vaccine.2006.04.054","volume":"24","author":"Y He","year":"2006","unstructured":"He, Y. et al. Identification and characterization of novel neutralizing epitopes in the receptor-binding domain of SARS-CoV spike protein: revealing the critical antigenic determinants in inactivated SARS-CoV vaccine. Vaccine 24, 5498\u20135508. https:\/\/doi.org\/10.1016\/j.vaccine.2006.04.054 (2006).","journal-title":"Vaccine"},{"key":"70864_CR76","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.vaccine.2009.09.126","volume":"28","author":"KL Johnson","year":"2009","unstructured":"Johnson, K. L., Ovsyannikova, I. G., Mason, C. J., Bergen, H. R. III. & Poland, G. A. Discovery of naturally processed and HLA-presented class I peptides from vaccinia virus infection using mass spectrometry for vaccine development. Vaccine 28, 38\u201347 (2009).","journal-title":"Vaccine"},{"key":"70864_CR77","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1021\/acschembio.6b00994","volume":"12","author":"L Zhang","year":"2017","unstructured":"Zhang, L. et al. Development of autologous C5 vaccine nanoparticles to reduce intravascular hemolysis in vivo. ACS Chem Biol. 12, 539\u2013547. https:\/\/doi.org\/10.1021\/acschembio.6b00994 (2017).","journal-title":"ACS Chem Biol."},{"key":"70864_CR78","doi-asserted-by":"publisher","first-page":"19234","DOI":"10.1038\/srep19234","volume":"6","author":"KD Brune","year":"2016","unstructured":"Brune, K. D. et al. Plug-and-display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization. Sci. Rep. 6, 19234. https:\/\/doi.org\/10.1038\/srep19234 (2016).","journal-title":"Sci. Rep."},{"key":"70864_CR79","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.antiviral.2017.09.012","volume":"147","author":"L Zhai","year":"2017","unstructured":"Zhai, L. et al. A novel candidate HPV vaccine: MS2 phage VLP displaying a tandem HPV L2 peptide offers similar protection in mice to Gardasil-9. Antiviral Res. 147, 116\u2013123. https:\/\/doi.org\/10.1016\/j.antiviral.2017.09.012 (2017).","journal-title":"Antiviral Res."},{"key":"70864_CR80","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1002\/wnan.1263","volume":"6","author":"DP McCarthy","year":"2014","unstructured":"McCarthy, D. P., Hunter, Z. N., Chackerian, B., Shea, L. D. & Miller, S. D. Targeted immunomodulation using antigen-conjugated nanoparticles. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 6, 298\u2013315. https:\/\/doi.org\/10.1002\/wnan.1263 (2014).","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"70864_CR81","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1002\/prot.20264","volume":"57","author":"Y Zhang","year":"2004","unstructured":"Zhang, Y. & Skolnick, J. Scoring function for automated assessment of protein structure template quality. Proteins 57, 702\u2013710. https:\/\/doi.org\/10.1002\/prot.20264 (2004).","journal-title":"Proteins"},{"key":"70864_CR82","doi-asserted-by":"publisher","first-page":"W431","DOI":"10.1093\/nar\/gkv495","volume":"43","author":"H Lee","year":"2015","unstructured":"Lee, H., Heo, L., Lee, M. S. & Seok, C. GalaxyPepDock: a protein-peptide docking tool based on interaction similarity and energy optimization. Nucl. Acids Res. 43, W431-435. https:\/\/doi.org\/10.1093\/nar\/gkv495 (2015).","journal-title":"Nucl. Acids Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-70864-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-70864-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-70864-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T03:50:15Z","timestamp":1696564215000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-70864-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,25]]},"references-count":82,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["70864"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-70864-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.05.14.093757","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,25]]},"assertion":[{"value":"20 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 August 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland offers consultative advice on vaccine development to Merck & Co., Medicago, GlaxoSmithKline, Sanofi Pasteur, Emergent Biosolutions, Dynavax, Genentech, Eli Lilly and Company, Janssen Global Services LLC, Kentucky Bioprocessing, and Genevant Sciences, Inc. Drs. Poland, Kennedy, and Ovsyannikova hold patents related to vaccinia, influenza, and measles peptide vaccines. Drs. Poland, Kennedy, and Ovsyannikova have received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. Dr. Kennedy has received funding from Merck Research Laboratories to study waning immunity to mumps vaccine. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. All other authors declare no competing financial interests. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14179"}}