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Biophysical and structural methods have become important tools for the rational design and engineering of improved antigen\u2010based vaccines. Vaccines containing <jats:italic>Leptospira<\/jats:italic> immunoglobulin\u2010like (Lig) protein\u2010derived antigens are currently the most promising candidates for protective immunity against the globally prevalent bacterial pathogen, \n<jats:italic>Leptospira interrogans<\/jats:italic>; however, vaccine trials using these domains have produced inconsistent results. Here, we compare the thermostability of domains from the main immunogenic regions from major leptospiral antigens, LigA and LigB. By measuring temperature\u2010dependent fluorescence decay of the hydrophobic core tryptophan, 17 individual Lig protein immunoglobulin\u2010like (Ig\u2010like) domains were shown to display a broad range of unfolding temperatures. For a majority of the domains, stability issues begin to occur at physiologically relevant temperatures. A set of chimeric Ig\u2010like domains was used to establish the ability of transplanted domain regions to enhance thermostability. Further insights into the determinants for domain stabilization were explored with nuclear magnetic resonance dynamics and mutational analysis. The current study has yielded a set of thermostable Ig\u2010like domain scaffolds for use in engineering antigen\u2010based vaccines and demonstrates the importance of incorporating thermostability screening as a design parameter.<\/jats:p>","DOI":"10.1002\/bit.26864","type":"journal-article","created":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T10:06:07Z","timestamp":1542017167000},"page":"260-271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Comparative screening of recombinant antigen thermostability for improved leptospirosis vaccine design"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2752-0367","authenticated-orcid":false,"given":"Christopher P.","family":"Ptak","sequence":"first","affiliation":[{"name":"Department of Population Medicine and Diagnostic Sciences College of Veterinary Medicine, Cornell University Ithaca New York"},{"name":"Department of 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