{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:31:10Z","timestamp":1787243470008,"version":"build-2736575974"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19fk0108113"],"award-info":[{"award-number":["JP19fk0108113"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["HHSN272201400008C"],"award-info":[{"award-number":["HHSN272201400008C"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["75N93019C00051"],"award-info":[{"award-number":["75N93019C00051"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001368","name":"V Foundation for Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001368","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bioengineering &amp; Transla Med"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The persistence of the global severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) pandemic has brought to the forefront the need for safe and effective vaccination strategies. In particular, the emergence of several variants with greater infectivity and resistance to current vaccines has motivated the development of a vaccine that elicits a broadly neutralizing immune response against all variants. In this study, we used a nanoparticle\u2010based vaccine platform for the multivalent display of the receptor\u2010binding domain (RBD) of the SARS\u2010CoV\u20102 spike (S) protein, the primary target of neutralizing antibodies. Multiple copies of RBD were conjugated to the SpyCatcher\u2010mi3 protein nanoparticle to produce a highly immunogenic nanoparticle\u2010based vaccine. RBD\u2010SpyCatcher\u2010mi3 vaccines elicited broadly cross\u2010reactive antibodies that recognized the spike proteins of not just an early isolate of SARS\u2010CoV\u20102, but also three SARS\u2010CoV\u20102 variants of concern as well as SARS\u2010CoV\u20101. Moreover, immunization elicited high neutralizing antibody titers against an early isolate of SARS\u2010CoV\u20102 as well as four variants of concern, including the delta variant. These results reveal the potential of RBD\u2010SpyCatcher\u2010mi3 as a broadly protective vaccination strategy.<\/jats:p>","DOI":"10.1002\/btm2.10253","type":"journal-article","created":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:13:25Z","timestamp":1630109605000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Potent neutralization of\n                    <scp>SARS\u2010CoV<\/scp>\n                    \u20102 including variants of concern by vaccines presenting the receptor\u2010binding domain multivalently from nanoscaffolds"],"prefix":"10.1002","volume":"6","author":[{"given":"Peter J.","family":"Halfmann","sequence":"first","affiliation":[{"name":"Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine University of Wisconsin  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Castro","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Loeffler","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Frey","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiho","family":"Chiba","sequence":"additional","affiliation":[{"name":"Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine University of Wisconsin  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Kawaoka","sequence":"additional","affiliation":[{"name":"Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine University of Wisconsin  Madison Wisconsin USA"},{"name":"Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science University of Tokyo  Tokyo Japan"},{"name":"Center for Global Viral Infections National Center for Global Health and Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3084-4098","authenticated-orcid":false,"given":"Ravi S.","family":"Kane","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,9]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"WHO Coronavirus (COVID\u201019) Dashboard.World Health Organization.https:\/\/covid19.who.int\/. Published2021.24 2021. Accessed June 24 2021."},{"issue":"7830","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/s41586-020-2798-3","article-title":"SARS\u2010CoV\u20102 vaccines in development","volume":"586","author":"Krammer F","year":"2020","journal-title":"Nature"},{"issue":"1","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"4541","DOI":"10.1038\/s41467-020-18319-6","article-title":"Molecular interaction and inhibition of SARS\u2010CoV\u20102 binding to the ACE2 receptor","volume":"11","author":"Yang J","year":"2020","journal-title":"Nat Commun"},{"issue":"6","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.immuni.2020.11.009","article-title":"SARS\u2010CoV\u20102 mRNA vaccines Foster potent antigen\u2010specific germinal center responses associated with neutralizing antibody generation","volume":"53","author":"Lederer K","year":"2020","journal-title":"Immunity"},{"issue":"1","key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/s41467-020-20654-7","article-title":"A COVID\u201019 vaccine candidate using SpyCatcher multimerization of the SARS\u2010CoV\u20102 spike protein receptor\u2010binding domain induces potent neutralising antibody responses","volume":"12","author":"Tan TK","year":"2021","journal-title":"Nat Commun"},{"issue":"2","key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"2738","DOI":"10.1021\/acsnano.0c08379","article-title":"Rapid development of SARS\u2010CoV\u20102 spike protein receptor\u2010binding domain self\u2010assembled nanoparticle vaccine candidates","volume":"15","author":"Kang Y\u2010F","year":"2021","journal-title":"ACS Nano"},{"issue":"6530","key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1126\/science.abf6840","article-title":"Mosaic nanoparticles elicit cross\u2010reactive immune responses to zoonotic coronaviruses in mice","volume":"371","author":"Cohen AA","year":"2021","journal-title":"Science"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/s41586-021-03594-0","article-title":"Neutralizing antibody vaccine for pandemic and pre\u2010emergent coronaviruses","volume":"594","author":"Saunders KO","year":"2021","journal-title":"Nature"},{"issue":"6510","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1126\/science.abc5881","article-title":"Structural basis for neutralization of SARS\u2010CoV\u20102 and SARS\u2010CoV by a potent therapeutic antibody","volume":"369","author":"Lv Z","year":"2020","journal-title":"Science"},{"issue":"7815","key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41586-020-2349-y","article-title":"Cross\u2010neutralization of SARS\u2010CoV\u20102 by a human monoclonal SARS\u2010CoV antibody","volume":"583","author":"Pinto D","year":"2020","journal-title":"Nature"},{"issue":"4","key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/d41587-021-00001-x","article-title":"Innovators target vaccines for variants and shortages in global south","volume":"39","author":"Sheridan C","year":"2021","journal-title":"Nat Biotechnol"},{"issue":"9","key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"8855","DOI":"10.1021\/acsnano.8b02805","article-title":"Engineering a rugged nanoscaffold to enhance plug\u2010and\u2010display vaccination","volume":"12","author":"Bruun TUJ","year":"2018","journal-title":"ACS Nano"},{"issue":"7819","key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/s41586-020-2380-z","article-title":"Human neutralizing antibodies elicited by SARS\u2010CoV\u20102 infection","volume":"584","author":"Ju B","year":"2020","journal-title":"Nature"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1101\/2021.07.19.452771"},{"issue":"6491","key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1126\/science.abb7269","article-title":"A highly conserved cryptic epitope in the receptor binding domains of SARS\u2010CoV\u20102 and SARS\u2010CoV","volume":"368","author":"Yuan M","year":"2020","journal-title":"Science"},{"issue":"7","key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1038\/s41591-020-0913-5","article-title":"A serological assay to detect SARS\u2010CoV\u20102 seroconversion in humans","volume":"26","author":"Amanat F","year":"2020","journal-title":"Nat Med"},{"issue":"13","key":"e_1_2_9_18_1","doi-asserted-by":"crossref","first-page":"7001","DOI":"10.1073\/pnas.2002589117","article-title":"Enhanced isolation of SARS\u2010CoV\u20102 by TMPRSS2\u2010expressing cells","volume":"117","author":"Matsuyama S","year":"2020","journal-title":"Proc Natl Acad Sci"}],"container-title":["Bioengineering &amp; Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btm2.10253","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/btm2.10253","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btm2.10253","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T20:32:36Z","timestamp":1760041956000},"score":1,"resource":{"primary":{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/10.1002\/btm2.10253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":17,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1002\/btm2.10253"],"URL":"https:\/\/doi.org\/10.1002\/btm2.10253","archive":["Portico"],"relation":{},"ISSN":["2380-6761","2380-6761"],"issn-type":[{"value":"2380-6761","type":"print"},{"value":"2380-6761","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9]]},"assertion":[{"value":"2021-07-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e10253"}}