{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:16:50Z","timestamp":1792660610630,"version":"4.5.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"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":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The COVID-19 pandemic continues to wreak havoc as worldwide SARS-CoV-2 infection, hospitalization, and death rates climb unabated. Effective vaccines remain the most promising approach to counter SARS-CoV-2. Yet, while promising results are emerging from COVID-19 vaccine trials, the need for multiple doses and the challenges associated with the widespread distribution and administration of vaccines remain concerns. Here, we engineered the coat protein of the MS2 bacteriophage and generated nanoparticles displaying multiple copies of the SARS-CoV-2 spike (S) protein. The use of these nanoparticles as vaccines generated high neutralizing antibody titers and protected Syrian hamsters from a challenge with SARS-CoV-2 after a single immunization with no infectious virus detected in the lungs. This nanoparticle-based vaccine platform thus provides protection after a single immunization and may be broadly applicable for protecting against SARS-CoV-2 and future pathogens with pandemic potential.<\/jats:p>","DOI":"10.1038\/s42003-021-02128-8","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T06:03:29Z","timestamp":1621404209000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Multivalent nanoparticle-based vaccines protect hamsters against SARS-CoV-2 after a single immunization"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0415-6013","authenticated-orcid":false,"given":"Shiho","family":"Chiba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1863-694X","authenticated-orcid":false,"given":"Steven J.","family":"Frey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Halfmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kuroda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Maemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2438-8156","authenticated-orcid":false,"given":"Jie E.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0712-9475","authenticated-orcid":false,"given":"Elizabeth R.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5061-8296","authenticated-orcid":false,"given":"Yoshihiro","family":"Kawaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3084-4098","authenticated-orcid":false,"given":"Ravi S.","family":"Kane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"2128_CR1","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1038\/s41586-020-2798-3","volume":"586","author":"F Krammer","year":"2020","unstructured":"Krammer, F. SARS-CoV-2 vaccines in development. Nature 586, 516\u2013527, https:\/\/doi.org\/10.1038\/s41586-020-2798-3 (2020).","journal-title":"Nature"},{"key":"2128_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18319-6","volume":"11","author":"J Yang","year":"2020","unstructured":"Yang, J. et al. Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor. Nat. Commun. 11, 4541, https:\/\/doi.org\/10.1038\/s41467-020-18319-6 (2020).","journal-title":"Nat. Commun."},{"key":"2128_CR3","doi-asserted-by":"publisher","unstructured":"Addetia, A. et al. Neutralizing antibodies correlate with protection from SARS-CoV-2 in humans during a fishery vessel outbreak with a high attack rate. J. Clin. Microbiol. https:\/\/doi.org\/10.1128\/JCM.02107-20 (2020).","DOI":"10.1128\/JCM.02107-20"},{"key":"2128_CR4","doi-asserted-by":"publisher","unstructured":"Walls, A. C. et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. https:\/\/doi.org\/10.1016\/j.cell.2020.02.058 (2020).","DOI":"10.1016\/j.cell.2020.02.058"},{"key":"2128_CR5","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1038\/s41565-020-0737-y","volume":"15","author":"MD Shin","year":"2020","unstructured":"Shin, M. D. et al. COVID-19 vaccine development and a potential nanomaterial path forward. Nat. Nanotechnol. 15, 646\u2013655, https:\/\/doi.org\/10.1038\/s41565-020-0737-y (2020).","journal-title":"Nat. Nanotechnol."},{"key":"2128_CR6","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/nri2868","volume":"10","author":"MF Bachmann","year":"2010","unstructured":"Bachmann, M. F. & Jennings, G. T. Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat. Rev. Immunol. 10, 787\u2013796, https:\/\/doi.org\/10.1038\/nri2868 (2010).","journal-title":"Nat. Rev. Immunol."},{"key":"2128_CR7","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.coviro.2016.03.001","volume":"18","author":"KM Frietze","year":"2016","unstructured":"Frietze, K. M., Peabody, D. S. & Chackerian, B. Engineering virus-like particles as vaccine platforms. Curr. Opin. Virol. 18, 44\u201349, https:\/\/doi.org\/10.1016\/j.coviro.2016.03.001 (2016).","journal-title":"Curr. Opin. Virol."},{"key":"2128_CR8","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1002\/wnan.119","volume":"3","author":"EM Plummer","year":"2011","unstructured":"Plummer, E. M. & Manchester, M. Viral nanoparticles and virus-like particles: platforms for contemporary vaccine design. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol 3, 174\u2013196, https:\/\/doi.org\/10.1002\/wnan.119 (2011).","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol"},{"key":"2128_CR9","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1146\/annurev.immunol.15.1.235","volume":"15","author":"MF Bachmann","year":"1997","unstructured":"Bachmann, M. F. & Zinkernagel, R. M. Neutralizing antiviral B cell responses. Annu Rev. Immunol. 15, 235\u2013270, https:\/\/doi.org\/10.1146\/annurev.immunol.15.1.235 (1997).","journal-title":"Annu Rev. Immunol."},{"key":"2128_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74949-2","volume":"10","author":"B Zhang","year":"2020","unstructured":"Zhang, B. et al. A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone. Sci. Rep. 10, 18149, https:\/\/doi.org\/10.1038\/s41598-020-74949-2 (2020).","journal-title":"Sci. Rep."},{"key":"2128_CR11","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/371623a0","volume":"371","author":"K Valegard","year":"1994","unstructured":"Valegard, K., Murray, J. B., Stockley, P. G., Stonehouse, N. J. & Liljas, L. Crystal structure of an RNA bacteriophage coat protein-operator complex. Nature 371, 623\u2013626, https:\/\/doi.org\/10.1038\/371623a0 (1994).","journal-title":"Nature"},{"key":"2128_CR12","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.jmb.2008.04.049","volume":"380","author":"DS Peabody","year":"2008","unstructured":"Peabody, D. S. et al. Immunogenic display of diverse peptides on virus-like particles of RNA phage MS2. J. Mol. Biol. 380, 252\u2013263, https:\/\/doi.org\/10.1016\/j.jmb.2008.04.049 (2008).","journal-title":"J. Mol. Biol."},{"key":"2128_CR13","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":"2128_CR14","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/s41586-020-2180-5","volume":"581","author":"J Lan","year":"2020","unstructured":"Lan, J. et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 581, 215\u2013220, https:\/\/doi.org\/10.1038\/s41586-020-2180-5 (2020).","journal-title":"Nature"},{"key":"2128_CR15","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/s41586-020-2380-z","volume":"584","author":"B Ju","year":"2020","unstructured":"Ju, B. et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature 584, 115\u2013119, https:\/\/doi.org\/10.1038\/s41586-020-2380-z (2020).","journal-title":"Nature"},{"key":"2128_CR16","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/s41586-020-2381-y","volume":"584","author":"R Shi","year":"2020","unstructured":"Shi, R. et al. A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature 584, 120\u2013124, https:\/\/doi.org\/10.1038\/s41586-020-2381-y (2020).","journal-title":"Nature"},{"key":"2128_CR17","doi-asserted-by":"publisher","first-page":"e237","DOI":"10.1371\/journal.pmed.0030237","volume":"3","author":"J ter Meulen","year":"2006","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).","journal-title":"PLoS Med"},{"key":"2128_CR18","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1126\/science.abd0826","volume":"369","author":"CL Hsieh","year":"2020","unstructured":"Hsieh, C. L. et al. Structure-based design of prefusion-stabilized SARS-CoV-2 spikes. Science 369, 1501\u20131505, https:\/\/doi.org\/10.1126\/science.abd0826 (2020).","journal-title":"Science"},{"key":"2128_CR19","doi-asserted-by":"publisher","first-page":"16587","DOI":"10.1073\/pnas.2009799117","volume":"117","author":"M Imai","year":"2020","unstructured":"Imai, M. et al. Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development. Proc. Natl Acad. Sci. USA 117, 16587\u201316595, https:\/\/doi.org\/10.1073\/pnas.2009799117 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2128_CR20","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/s41586-020-2342-5","volume":"583","author":"SF Sia","year":"2020","unstructured":"Sia, S. F. et al. Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature 583, 834\u2013838, https:\/\/doi.org\/10.1038\/s41586-020-2342-5 (2020).","journal-title":"Nature"},{"key":"2128_CR21","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.1038\/s41591-020-1070-6","volume":"26","author":"LH Tostanoski","year":"2020","unstructured":"Tostanoski, L. H. et al. Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters. Nat. Med 26, 1694\u20131700, https:\/\/doi.org\/10.1038\/s41591-020-1070-6 (2020).","journal-title":"Nat. Med"},{"key":"2128_CR22","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1038\/s41586-020-2622-0","volume":"586","author":"KS Corbett","year":"2020","unstructured":"Corbett, K. S. et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature 586, 567\u2013571, https:\/\/doi.org\/10.1038\/s41586-020-2622-0 (2020).","journal-title":"Nature"},{"key":"2128_CR23","doi-asserted-by":"publisher","first-page":"15307","DOI":"10.1039\/c9nr05145g","volume":"11","author":"A Arsiwala","year":"2019","unstructured":"Arsiwala, A. et al. Nanopatterning protein antigens to refocus the immune response. Nanoscale 11, 15307\u201315311, https:\/\/doi.org\/10.1039\/c9nr05145g (2019).","journal-title":"Nanoscale"},{"key":"2128_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-021-00321-8","volume":"6","author":"Q Jia","year":"2021","unstructured":"Jia, Q. et al. Replicating bacterium-vectored vaccine expressing SARS-CoV-2 Membrane and Nucleocapsid proteins protects against severe COVID-19-like disease in hamsters. NPJ Vaccines 6, 47, https:\/\/doi.org\/10.1038\/s41541-021-00321-8 (2021).","journal-title":"NPJ Vaccines"},{"key":"2128_CR25","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/s41586-020-3035-9","volume":"590","author":"L Sanchez-Felipe","year":"2021","unstructured":"Sanchez-Felipe, L. et al. A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate. Nature 590, 320\u2013325, https:\/\/doi.org\/10.1038\/s41586-020-3035-9 (2021).","journal-title":"Nature"},{"key":"2128_CR26","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.jmb.2013.09.016","volume":"426","author":"M Fairhead","year":"2014","unstructured":"Fairhead, M., Krndija, D., Lowe, E. D. & Howarth, M. Plug-and-play pairing via defined divalent streptavidins. J. Mol. Biol. 426, 199\u2013214, https:\/\/doi.org\/10.1016\/j.jmb.2013.09.016 (2014).","journal-title":"J. Mol. Biol."},{"key":"2128_CR27","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1038\/nprot.2008.20","volume":"3","author":"M Howarth","year":"2008","unstructured":"Howarth, M. & Ting, A. Y. Imaging proteins in live mammalian cells with biotin ligase and monovalent streptavidin. Nat. Protoc. 3, 534\u2013545, https:\/\/doi.org\/10.1038\/nprot.2008.20 (2008).","journal-title":"Nat. Protoc."},{"key":"2128_CR28","doi-asserted-by":"publisher","unstructured":"Booth, D. S., Avila-Sakar, A. & Cheng, Y. Visualizing proteins and macromolecular complexes by negative stain EM: from grid preparation to image acquisition. J. Vis. Exp. https:\/\/doi.org\/10.3791\/3227 (2011).","DOI":"10.3791\/3227"},{"key":"2128_CR29","doi-asserted-by":"publisher","unstructured":"Jung, M. K. & Mun, J. Y. Sample preparation and imaging of exosomes by transmission electron microscopy. J. Vis. Exp. https:\/\/doi.org\/10.3791\/56482 (2018).","DOI":"10.3791\/56482"},{"key":"2128_CR30","doi-asserted-by":"publisher","unstructured":"Yang, J. E., Larson, M. R., Sibert, B. S., Shrum, S. & Wright, E. R. CorRelator: Interactive software for real-time high precision cryo-correlative light and electron microscopy. J. Struct. Biol. https:\/\/doi.org\/10.1016\/j.jsb.2021.107709 (2021).","DOI":"10.1016\/j.jsb.2021.107709"},{"key":"2128_CR31","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":"2128_CR32","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nmeth.4193","volume":"14","author":"SQ Zheng","year":"2017","unstructured":"Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331\u2013332, https:\/\/doi.org\/10.1038\/nmeth.4193 (2017).","journal-title":"Nat. Methods"},{"key":"2128_CR33","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.jsb.2015.04.016","volume":"190","author":"JG Galaz-Montoya","year":"2015","unstructured":"Galaz-Montoya, J. G., Flanagan, J., Schmid, M. F. & Ludtke, S. J. Single particle tomography in EMAN2. J. Struct. Biol. 190, 279\u2013290, https:\/\/doi.org\/10.1016\/j.jsb.2015.04.016 (2015).","journal-title":"J. Struct. Biol."},{"key":"2128_CR34","doi-asserted-by":"publisher","first-page":"7001","DOI":"10.1073\/pnas.2002589117","volume":"117","author":"S Matsuyama","year":"2020","unstructured":"Matsuyama, S. et al. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc. Natl Acad. Sci. USA 117, 7001\u20137003, https:\/\/doi.org\/10.1073\/pnas.2002589117 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02128-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02128-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02128-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T14:18:58Z","timestamp":1670077138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02128-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,19]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["2128"],"URL":"https:\/\/doi.org\/10.1038\/s42003-021-02128-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-121208\/v1","asserted-by":"object"}]},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,19]]},"assertion":[{"value":"29 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"597"}}