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By taking advantage of such interactions of the norovirus shell (S) domain that naturally builds the interior shells of norovirus capsids, we have developed a technology to produce 60-valent, icosahedral S60 nanoparticles through the E. coli system. This has been achieved by several modifications to the S domain, including an R69A mutation to destruct an exposed proteinase cleavage site and triple cysteine mutations (V57C\/Q58C\/S136C) to establish inter-S domain disulfide bonds for enhanced inter-S domain interactions. The polyvalent S60 nanoparticle with 60 exposed S domain C-termini offers an ideal platform for antigen presentation, leading to enhanced immunogenicity to the surface-displayed antigens for vaccine development. This was proven by constructing a chimeric S60 nanoparticle displaying 60 rotavirus (RV) VP8* proteins, the major RV-neutralizing antigen. These S60-VP8* particles are easily produced and elicited high IgG response in mice toward the displayed VP8* antigens. The mouse antisera after immunization with the S60-VP8* particles exhibited high blockades against RV VP8* binding to its glycan ligands and high neutralizing activities against RV infection in culture cells. The three-dimensional structures of the S60 and S60-VP8* particles were studied. Furthermore, the S60 nanoparticle can display other antigens, supporting the notion that the S60 nanoparticle is a multifunctional vaccine platform. Finally, the intermolecular disulfide bond approach may be used to stabilize other viral-like particles to display foreign antigens for vaccine development.<\/jats:p>","DOI":"10.1021\/acsnano.8b02776","type":"journal-article","created":{"date-parts":[[2018,9,20]],"date-time":"2018-09-20T14:23:34Z","timestamp":1537453414000},"page":"10665-10682","source":"Crossref","is-referenced-by-count":44,"title":["Bioengineered\nNorovirus S60 Nanoparticles\nas a Multifunctional Vaccine Platform"],"prefix":"10.1021","volume":"12","author":[{"given":"Ming","family":"Xia","sequence":"first","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center , , , ,","place":["Cincinnati, Ohio, United States, 45229"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengwei","family":"Huang","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center , , , ,","place":["Cincinnati, Ohio, United States, 45229"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Sun","sequence":"additional","affiliation":[{"name":"Purdue University , , , ,","place":["West Lafayette, Indiana, United States, 47907"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Han","sequence":"additional","affiliation":[{"name":"University of Alberta , , ,","place":["Alberta, Canada, T6G 2G2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank S.","family":"Vago","sequence":"additional","affiliation":[{"name":"Purdue University , , , ,","place":["West Lafayette, Indiana, United States, 47907"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunpeng","family":"Li","sequence":"additional","affiliation":[{"name":"Purdue University , , , ,","place":["West Lafayette, Indiana, United States, 47907"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Zhong","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center , , , ,","place":["Cincinnati, Ohio, United States, 45229"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Purdue University , , , ,","place":["West Lafayette, Indiana, United States, 47907"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3389-7112","authenticated-orcid":true,"given":"John S.","family":"Klassen","sequence":"additional","affiliation":[{"name":"University of Alberta , , ,","place":["Alberta, Canada, T6G 2G2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center , , , ,","place":["Cincinnati, Ohio, United States, 45229"]},{"name":"University of Cincinnati College of Medicine , , , ,","place":["Cincinnati, Ohio, United States, 45229"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6489-5507","authenticated-orcid":true,"given":"Ming","family":"Tan","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center , , , ,","place":["Cincinnati, Ohio, United States, 45229"]},{"name":"University of Cincinnati College of Medicine , , , ,","place":["Cincinnati, Ohio, United States, 45229"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2018,9,20]]},"reference":[{"key":"2026081801082145400_cit1","doi-asserted-by":"publisher","first-page":"889","DOI":"10.2217\/nnm.12.62","article-title":"Norovirus P Particle:\nA Subviral Nanoparticle for Vaccine Development\nagainst Norovirus, Rotavirus and Influenza Virus","volume":"7","author":"Tan","year":"2012","journal-title":"Nanomedicine (London, U. 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