{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:52:17Z","timestamp":1785894737416,"version":"3.56.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T00:00:00Z","timestamp":1603411200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T00:00:00Z","timestamp":1603411200000},"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>\n                    Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens is often complicated by inefficiencies in their production. To alleviate this issue, we developed a plug-and-play platform using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the 60-subunit\n                    <jats:italic>Aquifex aeolicus<\/jats:italic>\n                    lumazine synthase (LuS) and the 24-subunit\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    ferritin. LuS and ferritin coupled to SpyTag expressed well in a mammalian expression system when an\n                    <jats:italic>N-<\/jats:italic>\n                    linked glycan was added to the nanoparticle surface. The respiratory syncytial virus fusion (F) glycoprotein trimer\u2014stabilized in the prefusion conformation and fused with SpyCatcher\u2014could be efficiently conjugated to LuS-SpyTag or ferritin-SpyTag, enabling multivalent display of F trimers with prefusion antigenicity. Similarly, F-glycoprotein trimers from human parainfluenza virus-type 3 and spike-glycoprotein trimers from SARS-CoV-2 could be displayed on LuS nanoparticles with decent yield and antigenicity. Notably, murine vaccination with 0.08 \u00b5g of SARS-CoV-2 spike-LuS nanoparticle elicited\u00a0similar neutralizing responses as 2.0 \u00b5g of spike, which was\u2009~\u200925-fold higher\u00a0on a\u00a0weight-per-weight basis. The versatile platform described here thus allows for multivalent plug-and-play presentation on self-assembling nanoparticles of trimeric viral antigens, with SARS-CoV-2 spike-LuS nanoparticles inducing particularly potent neutralizing responses.\n                  <\/jats:p>","DOI":"10.1038\/s41598-020-74949-2","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T06:06:00Z","timestamp":1603433160000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone"],"prefix":"10.1038","volume":"10","author":[{"given":"Baoshan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara W.","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaroslav","family":"Tsybovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olubukola M.","family":"Abiona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey B.","family":"Hutchinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan I.","family":"Moliva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S.","family":"Olia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amarendra","family":"Pegu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Phung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume B. E.","family":"Stewart-Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaello","family":"Verardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingshu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuishu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Werner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Sung","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Yap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongqing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Mascola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barney S.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kizzmekia S.","family":"Corbett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Kwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,23]]},"reference":[{"key":"74949_CR1","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.csbj.2015.11.001","volume":"14","author":"J Lopez-Sagaseta","year":"2016","unstructured":"Lopez-Sagaseta, J., Malito, E., Rappuoli, R. & Bottomley, M. J. Self-assembling protein nanoparticles in the design of vaccines. Comput. Struct. Biotechnol. J. 14, 58\u201368. https:\/\/doi.org\/10.1016\/j.csbj.2015.11.001 (2016).","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"74949_CR2","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/nature12202","volume":"499","author":"M Kanekiyo","year":"2013","unstructured":"Kanekiyo, M. et al. Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature 499, 102\u2013106. https:\/\/doi.org\/10.1038\/nature12202 (2013).","journal-title":"Nature"},{"key":"74949_CR3","doi-asserted-by":"publisher","unstructured":"3Marcandalli, J. et al. Induction of potent neutralizing antibody responses by a designed protein nanoparticle vaccine for respiratory syncytial virus. Cell 176, 1420\u20131431 e1417, https:\/\/doi.org\/10.1016\/j.cell.2019.01.046 (2019).","DOI":"10.1016\/j.cell.2019.01.046"},{"key":"74949_CR4","doi-asserted-by":"publisher","unstructured":"4Swanson, K. A. et al. A respiratory syncytial virus (RSV) F protein nanoparticle vaccine focuses antibody responses to a conserved neutralization domain. Sci. Immunol. 5, https:\/\/doi.org\/10.1126\/sciimmunol.aba6466 (2020).","DOI":"10.1126\/sciimmunol.aba6466"},{"key":"74949_CR5","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1038\/mt.2015.227","volume":"24","author":"C Cavelti-Weder","year":"2016","unstructured":"Cavelti-Weder, C. et al. Development of an interleukin-1beta vaccine in patients with type 2 diabetes. Mol. Ther. 24, 1003\u20131012. https:\/\/doi.org\/10.1038\/mt.2015.227 (2016).","journal-title":"Mol. Ther."},{"key":"74949_CR6","doi-asserted-by":"publisher","first-page":"e2547","DOI":"10.1371\/journal.pone.0002547","volume":"3","author":"J Cornuz","year":"2008","unstructured":"Cornuz, J. et al. A vaccine against nicotine for smoking cessation: A randomized controlled trial. PLoS ONE 3, e2547. https:\/\/doi.org\/10.1371\/journal.pone.0002547 (2008).","journal-title":"PLoS ONE"},{"key":"74949_CR7","doi-asserted-by":"publisher","first-page":"E690","DOI":"10.1073\/pnas.1115485109","volume":"109","author":"B Zakeri","year":"2012","unstructured":"Zakeri, B. et al. Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin. Proc. Natl. Acad. Sci. U S A 109, E690-697. https:\/\/doi.org\/10.1073\/pnas.1115485109 (2012).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"74949_CR8","doi-asserted-by":"publisher","first-page":"2931","DOI":"10.3389\/fimmu.2019.02931","volume":"10","author":"A Marini","year":"2019","unstructured":"Marini, A. et al. A Universal plug-and-display vaccine carrier based on HBsAg VLP to maximize effective antibody response. Front. Immunol. 10, 2931. https:\/\/doi.org\/10.3389\/fimmu.2019.02931 (2019).","journal-title":"Front. Immunol."},{"key":"74949_CR9","doi-asserted-by":"publisher","first-page":"12041","DOI":"10.1038\/ncomms12041","volume":"7","author":"L He","year":"2016","unstructured":"He, L. et al. Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles. Nat. Commun. 7, 12041. https:\/\/doi.org\/10.1038\/ncomms12041 (2016).","journal-title":"Nat. Commun."},{"key":"74949_CR10","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/nm.3927","volume":"21","author":"HM Yassine","year":"2015","unstructured":"Yassine, H. M. et al. Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat. Med. 21, 1065\u20131070. https:\/\/doi.org\/10.1038\/nm.3927 (2015).","journal-title":"Nat. Med."},{"key":"74949_CR11","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1038\/s41586-019-1250-z","volume":"570","author":"A Escolano","year":"2019","unstructured":"Escolano, A. et al. Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques. Nature 570, 468\u2013473. https:\/\/doi.org\/10.1038\/s41586-019-1250-z (2019).","journal-title":"Nature"},{"key":"74949_CR12","doi-asserted-by":"publisher","first-page":"6405","DOI":"10.1016\/j.vaccine.2019.09.004","volume":"37","author":"ML Govasli","year":"2019","unstructured":"Govasli, M. L., Diaz, Y. & Puntervoll, P. Virus-like particle-display of the enterotoxigenic Escherichia coli heat-stable toxoid STh-A14T elicits neutralizing antibodies in mice. Vaccine 37, 6405\u20136414. https:\/\/doi.org\/10.1016\/j.vaccine.2019.09.004 (2019).","journal-title":"Vaccine"},{"key":"74949_CR13","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1186\/s12936-016-1574-1","volume":"15","author":"CM Janitzek","year":"2016","unstructured":"Janitzek, C. M. et al. Bacterial superglue generates a full-length circumsporozoite protein virus-like particle vaccine capable of inducing high and durable antibody responses. Malar. J. 15, 545. https:\/\/doi.org\/10.1186\/s12936-016-1574-1 (2016).","journal-title":"Malar. J."},{"key":"74949_CR14","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s12951-016-0181-1","volume":"14","author":"S Thrane","year":"2016","unstructured":"Thrane, S. et al. Bacterial superglue enables easy development of efficient virus-like particle based vaccines. J. Nanobiotechnol. 14, 30. https:\/\/doi.org\/10.1186\/s12951-016-0181-1 (2016).","journal-title":"J. Nanobiotechnol."},{"key":"74949_CR15","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":"74949_CR16","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.nano.2018.11.009","volume":"16","author":"W Wang","year":"2019","unstructured":"Wang, W. et al. Ferritin nanoparticle-based SpyTag\/SpyCatcher-enabled click vaccine for tumor immunotherapy. Nanomedicine 16, 69\u201378. https:\/\/doi.org\/10.1016\/j.nano.2018.11.009 (2019).","journal-title":"Nanomedicine"},{"key":"74949_CR17","doi-asserted-by":"publisher","unstructured":"17Duan, H. et al. Glycan masking focuses immune responses to the HIV-1 CD4-binding site and enhances elicitation of VRC01-class precursor antibodies. Immunity 49, 301\u2013311 e305, https:\/\/doi.org\/10.1016\/j.immuni.2018.07.005 (2018).","DOI":"10.1016\/j.immuni.2018.07.005"},{"key":"74949_CR18","doi-asserted-by":"publisher","first-page":"14002","DOI":"10.1128\/JVI.02614-14","volume":"88","author":"J Ingale","year":"2014","unstructured":"Ingale, J. et al. Hyperglycosylated stable core immunogens designed to present the CD4 binding site are preferentially recognized by broadly neutralizing antibodies. J. Virol. 88, 14002\u201314016. https:\/\/doi.org\/10.1128\/JVI.02614-14 (2014).","journal-title":"J. Virol."},{"key":"74949_CR19","doi-asserted-by":"publisher","first-page":"5889","DOI":"10.1128\/JVI.77.10.5889-5901.2003","volume":"77","author":"R Pantophlet","year":"2003","unstructured":"Pantophlet, R., Wilson, I. A. & Burton, D. R. Hyperglycosylated mutants of human immunodeficiency virus (HIV) type 1 monomeric gp120 as novel antigens for HIV vaccine design. J. Virol. 77, 5889\u20135901 (2003).","journal-title":"J. Virol."},{"key":"74949_CR20","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1016\/j.cell.2018.02.054","volume":"172","author":"FA Rey","year":"2018","unstructured":"Rey, F. A. & Lok, S. M. Common features of enveloped viruses and implications for immunogen design for next-generation vaccines. Cell 172, 1319\u20131334. https:\/\/doi.org\/10.1016\/j.cell.2018.02.054 (2018).","journal-title":"Cell"},{"key":"74949_CR21","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1126\/science.1243283","volume":"342","author":"JS McLellan","year":"2013","unstructured":"McLellan, J. S. et al. Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science 342, 592\u2013598. https:\/\/doi.org\/10.1126\/science.1243283 (2013).","journal-title":"Science"},{"key":"74949_CR22","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.cell.2016.04.010","volume":"165","author":"GB Stewart-Jones","year":"2016","unstructured":"Stewart-Jones, G. B. et al. Trimeric HIV-1-Env Structures Define Glycan Shields From Clades A, B, and G. Cell 165, 813\u2013826. https:\/\/doi.org\/10.1016\/j.cell.2016.04.010 (2016).","journal-title":"Cell"},{"key":"74949_CR23","doi-asserted-by":"publisher","unstructured":"23Walls, A. C. et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181, 281\u2013292 e286, https:\/\/doi.org\/10.1016\/j.cell.2020.02.058 (2020).","DOI":"10.1016\/j.cell.2020.02.058"},{"key":"74949_CR24","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":"74949_CR25","doi-asserted-by":"crossref","unstructured":"Zhang, X., Meining, W., Fischer, M., Bacher, A. & Ladenstein, R. X-ray structure analysis and crystallographic refinement of lumazine synthase from the hyperthermophile Aquifex aeolicus at 1.6 A resolution: Determinants of thermostability revealed from structural comparisons. J. Mol. Biol. 306, 1099-1114, 10.1006\/jmbi.2000.4435 (2001).","DOI":"10.1006\/jmbi.2000.4435"},{"key":"74949_CR26","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.jmb.2009.04.078","volume":"390","author":"KJ Cho","year":"2009","unstructured":"Cho, K. J. et al. The crystal structure of ferritin from Helicobacter pylori reveals unusual conformational changes for iron uptake. J. Mol. Biol. 390, 83\u201398. https:\/\/doi.org\/10.1016\/j.jmb.2009.04.078 (2009).","journal-title":"J. Mol. Biol."},{"key":"74949_CR27","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.cbpa.2015.10.002","volume":"29","author":"SC Reddington","year":"2015","unstructured":"Reddington, S. C. & Howarth, M. Secrets of a covalent interaction for biomaterials and biotechnology: SpyTag and SpyCatcher. Curr. Opin. Chem. Biol. 29, 94\u201399. https:\/\/doi.org\/10.1016\/j.cbpa.2015.10.002 (2015).","journal-title":"Curr. Opin. Chem. Biol."},{"key":"74949_CR28","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1126\/science.aad9195","volume":"351","author":"JG Jardine","year":"2016","unstructured":"Jardine, J. G. et al. HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen. Science 351, 1458\u20131463. https:\/\/doi.org\/10.1126\/science.aad9195 (2016).","journal-title":"Science"},{"key":"74949_CR29","doi-asserted-by":"publisher","unstructured":"Corbett, K. S. et al. Design of nanoparticulate group 2 influenza virus hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages. mBio 10, https:\/\/doi.org\/10.1128\/mBio.02810-18 (2019).","DOI":"10.1128\/mBio.02810-18"},{"key":"74949_CR30","doi-asserted-by":"publisher","unstructured":"Darricarrere, N. et al. Development of a pan-H1 influenza vaccine. J. Virol. 92, https:\/\/doi.org\/10.1128\/JVI.01349-18 (2018).","DOI":"10.1128\/JVI.01349-18"},{"key":"74949_CR31","doi-asserted-by":"publisher","unstructured":"Morris, C. D. et al. Differential antibody responses to conserved HIV-1 neutralizing epitopes in the context of multivalent Scaffolds and native-like gp140 trimers. mBio 8, https:\/\/doi.org\/10.1128\/mBio.00036-17 (2017).","DOI":"10.1128\/mBio.00036-17"},{"key":"74949_CR32","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.coi.2019.03.005","volume":"59","author":"BS Graham","year":"2019","unstructured":"Graham, B. S. Immunological goals for respiratory syncytial virus vaccine development. Curr. Opin. Immunol. 59, 57\u201364. https:\/\/doi.org\/10.1016\/j.coi.2019.03.005 (2019).","journal-title":"Curr. Opin. Immunol."},{"key":"74949_CR33","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1038\/nsmb.3267","volume":"23","author":"MG Joyce","year":"2016","unstructured":"Joyce, M. G. et al. Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV. Nat. Struct. Mol. Biol. 23, 811\u2013820. https:\/\/doi.org\/10.1038\/nsmb.3267 (2016).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"74949_CR34","doi-asserted-by":"publisher","first-page":"12265","DOI":"10.1073\/pnas.1811980115","volume":"115","author":"GBE Stewart-Jones","year":"2018","unstructured":"Stewart-Jones, G. B. E. et al. Structure-based design of a quadrivalent fusion glycoprotein vaccine for human parainfluenza virus types 1\u20134. Proc. Natl. Acad. Sci. U S A 115, 12265\u201312270. https:\/\/doi.org\/10.1073\/pnas.1811980115 (2018).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"74949_CR35","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1056\/NEJMoa1500245","volume":"373","author":"S Jain","year":"2015","unstructured":"Jain, S. et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N. Engl. J. Med. 373, 415\u2013427. https:\/\/doi.org\/10.1056\/NEJMoa1500245 (2015).","journal-title":"N. Engl. J. Med."},{"key":"74949_CR36","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1056\/NEJMoa1405870","volume":"372","author":"S Jain","year":"2015","unstructured":"Jain, S. et al. Community-acquired pneumonia requiring hospitalization among U.S. children. N. Engl. J. Med. 372, 835\u2013845. https:\/\/doi.org\/10.1056\/NEJMoa1405870 (2015).","journal-title":"N. Engl. J. Med."},{"key":"74949_CR37","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":"74949_CR38","doi-asserted-by":"publisher","unstructured":"Zhou, T. et al. Structure-based design with tag-based purification and in-process biotinylation enable streamlined development of SARS-CoV-2 spike molecular probes. bioRxiv: 2020.06.22.166033, https:\/\/doi.org\/10.1101\/2020.06.22.166033 (2020).","DOI":"10.1101\/2020.06.22.166033"},{"key":"74949_CR39","doi-asserted-by":"publisher","unstructured":"ter Meulen, J. et al. Human monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. PLoS Med 3, e237, https:\/\/doi.org\/10.1371\/journal.pmed.0030237 (2006).","DOI":"10.1371\/journal.pmed.0030237"},{"key":"74949_CR40","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb7269","author":"M Yuan","year":"2020","unstructured":"Yuan, M. et al. A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV. Science https:\/\/doi.org\/10.1126\/science.abb7269 (2020).","journal-title":"Science"},{"key":"74949_CR41","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2622-0","author":"KS Corbett","year":"2020","unstructured":"Corbett, K. S. et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature https:\/\/doi.org\/10.1038\/s41586-020-2622-0 (2020).","journal-title":"Nature"},{"key":"74949_CR42","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S0140-6736(15)60721-8","volume":"386","author":"SCTP Rts","year":"2015","unstructured":"Rts, S. C. T. P. Efficacy and safety of RTS, S\/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: Final results of a phase 3, individually randomised, controlled trial. Lancet 386, 31\u201345. https:\/\/doi.org\/10.1016\/S0140-6736(15)60721-8 (2015).","journal-title":"Lancet"},{"key":"74949_CR43","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1006\/jmbi.1994.1595","volume":"242","author":"VP Efimov","year":"1994","unstructured":"Efimov, V. P. et al. Fibritin encoded by bacteriophage T4 gene wac has a parallel triple-stranded alpha-helical coiled-coil structure. J. Mol. Biol. 242, 470\u2013486. https:\/\/doi.org\/10.1006\/jmbi.1994.1595 (1994).","journal-title":"J. Mol. Biol."},{"key":"74949_CR44","doi-asserted-by":"publisher","unstructured":"Walls, A. C. et al. Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2. bioRxiv:2020.08.11.247395, https:\/\/doi.org\/10.1101\/2020.08.11.247395 (2020).","DOI":"10.1101\/2020.08.11.247395"},{"key":"74949_CR45","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.jsb.2005.07.007","volume":"152","author":"DN Mastronarde","year":"2005","unstructured":"Mastronarde, D. N. Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36\u201351. https:\/\/doi.org\/10.1016\/j.jsb.2005.07.007 (2005).","journal-title":"J. Struct. Biol."},{"key":"74949_CR46","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.jsb.2012.09.006","volume":"180","author":"SH Scheres","year":"2012","unstructured":"Scheres, S. H. RELION: Implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519\u2013530. https:\/\/doi.org\/10.1016\/j.jsb.2012.09.006 (2012).","journal-title":"J. Struct. Biol."},{"key":"74949_CR47","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1006\/jsbi.1996.0030","volume":"116","author":"J Frank","year":"1996","unstructured":"Frank, J. et al. SPIDER and WEB: Processing and visualization of images in 3D electron microscopy and related fields. J. Struct. Biol. 116, 190\u2013199. https:\/\/doi.org\/10.1006\/jsbi.1996.0030 (1996).","journal-title":"J. Struct. Biol."},{"key":"74949_CR48","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jsb.2006.05.009","volume":"157","author":"G Tang","year":"2007","unstructured":"Tang, G. et al. EMAN2: An extensible image processing suite for electron microscopy. J. Struct. Biol. 157, 38\u201346. https:\/\/doi.org\/10.1016\/j.jsb.2006.05.009 (2007).","journal-title":"J. Struct. Biol."},{"key":"74949_CR49","doi-asserted-by":"publisher","first-page":"E7348","DOI":"10.1073\/pnas.1707304114","volume":"114","author":"J Pallesen","year":"2017","unstructured":"Pallesen, J. et al. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc. Natl. Acad. Sci. U S A 114, E7348\u2013E7357. https:\/\/doi.org\/10.1073\/pnas.1707304114 (2017).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"74949_CR50","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024671","author":"KS Corbett","year":"2020","unstructured":"Corbett, K. S. et al. Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. N. Engl. J. Med. https:\/\/doi.org\/10.1056\/NEJMoa2024671 (2020).","journal-title":"N. Engl. J. Med."},{"key":"74949_CR51","doi-asserted-by":"publisher","first-page":"9896","DOI":"10.1128\/JVI.01118-06","volume":"80","author":"E Bottcher","year":"2006","unstructured":"Bottcher, E. et al. Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium. J. Virol. 80, 9896\u20139898. https:\/\/doi.org\/10.1128\/JVI.01118-06 (2006).","journal-title":"J. Virol."},{"key":"74949_CR52","doi-asserted-by":"publisher","first-page":"7712","DOI":"10.1038\/ncomms8712","volume":"6","author":"L Wang","year":"2015","unstructured":"Wang, L. et al. Evaluation of candidate vaccine approaches for MERS-CoV. Nat. Commun. 6, 7712. https:\/\/doi.org\/10.1038\/ncomms8712 (2015).","journal-title":"Nat. Commun."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-74949-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-74949-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-74949-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T17:01:26Z","timestamp":1670346086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-74949-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,23]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["74949"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-74949-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.06.11.147496","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,23]]},"assertion":[{"value":"11 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 October 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"K.S.C. and B.S.G. are inventors on International Patent Application No. WO\/2018\/081318 entitled \u201cPrefusion Coronavirus Spike Proteins and Their Use.\u201d K.S.C., O.M.A., G.B.H., and B.S.G. are inventors on US Patent Application No. 62\/972,886 entitled \u201c2019-nCoV Vaccine\u201d. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18149"}}