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Conjugate vaccines are inherently expensive due to laborious manufacturing steps. Here, this work develops a particulate vaccine platform based on using engineered <jats:italic>Escherichia coli<\/jats:italic> to assemble CRM197\u2010antigen fusion proteins into discrete submicron\u2010sized particles. This approach enables precise loading of diverse antigens and epitopes enhancing their immunogenicity. A cost\u2010effective, high\u2010yield, and scalable biomanufacturing process is developed. Purified particulate CRM197\u2010antigen vaccines are ambient\u2010temperature stable. CRM197 particles incorporating pathogen\u2010specific antigens or epitopes from SARS\u2010CoV\u20102, <jats:italic>Streptococcus pyogenes<\/jats:italic> (group A), and <jats:italic>Mycobacterium tuberculosis<\/jats:italic> induced cell\u2010mediated and humoral immune responses mediating protective immunity in respective animal models of infection. The CRM197 particle vaccine platform is versatile, enabling co\u2010delivery of selected antigens\/epitopes together with immunogenic CRM197 as discrete stable particles avoiding laborious manufacture of soluble CRM197 and antigen followed by chemical conjugation.<\/jats:p>","DOI":"10.1002\/smll.202205819","type":"journal-article","created":{"date-parts":[[2022,12,24]],"date-time":"2022-12-24T03:33:07Z","timestamp":1671852787000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Assembly of Immunogenic Protein Particles toward Advanced Synthetic Vaccines"],"prefix":"10.1002","volume":"19","author":[{"given":"Shuxiong","family":"Chen","sequence":"first","affiliation":[{"name":"Centre for Cell Factories and Biopolymers Griffith Institute for Drug Discovery Griffith University  Brisbane Queensland 4111 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana H.","family":"Quan","sequence":"additional","affiliation":[{"name":"Centenary Institute The University of Sydney  Sydney New South Wales 2050 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayathri","family":"Sam","sequence":"additional","affiliation":[{"name":"Centre for Cell Factories and Biopolymers Griffith Institute for Drug Discovery Griffith University  Brisbane Queensland 4111 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Ozberk","sequence":"additional","affiliation":[{"name":"Institute for Glycomics Griffith University  Gold Coast Queensland 4215 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan T.","family":"Wang","sequence":"additional","affiliation":[{"name":"Centenary Institute The University of Sydney  Sydney New South Wales 2050 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Halfmann","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences School of Veterinary Medicine University of Wisconsin\u2010Madison  Madison WI 53706 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Pandey","sequence":"additional","affiliation":[{"name":"Institute for Glycomics Griffith University  Gold Coast Queensland 4215 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Good","sequence":"additional","affiliation":[{"name":"Institute for Glycomics Griffith University  Gold Coast Queensland 4215 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Kawaoka","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences School of Veterinary Medicine University of Wisconsin\u2010Madison  Madison WI 53706 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warwick J.","family":"Britton","sequence":"additional","affiliation":[{"name":"Centenary Institute The University of Sydney  Sydney New South Wales 2050 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3908-8903","authenticated-orcid":false,"given":"Bernd H. 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