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We report the conversion of Caf1 from a polymer to a monomer by circular permutation of the gene. Biophysical evaluation confirmed that the engineered Caf1 was a folded monomer. We compared the immunogenicity of the engineered monomer with polymeric Caf1 in antigen presentation assays to CD4 T-cell hybridomas in vitro, as well as in the induction of antibody responses and protection against subcutaneous challenge with<jats:italic>Y. pestis<\/jats:italic>in vivo. In C57BL\/6 mice, for which the major<jats:italic>H-2<\/jats:italic><jats:sup><jats:italic>b<\/jats:italic><\/jats:sup>-restricted immunodominant CD4 T-cell epitopes were intact in the engineered monomer, immunogenicity and protective efficacy were preserved, although antibody titers were decreased 10-fold. Disruption of an<jats:italic>H-2<\/jats:italic><jats:sup><jats:italic>d<\/jats:italic><\/jats:sup>-restricted immunodominant CD4 T-cell epitope during circular permutation resulted in a compromised T-cell response, a low postvaccination antibody titer, and a lack of protection of BALB\/c mice. The use of circular permutation in vaccine design has not been reported previously.<\/jats:p>","DOI":"10.1128\/iai.00437-06","type":"journal-article","created":{"date-parts":[[2006,11,21]],"date-time":"2006-11-21T01:05:37Z","timestamp":1164071137000},"page":"6624-6631","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Immunogenicity of a<i>Yersinia pestis<\/i>Vaccine Antigen Monomerized by Circular Permutation"],"prefix":"10.1128","volume":"74","author":[{"given":"David A.","family":"Chalton","sequence":"first","affiliation":[{"name":"Institute for Cell and Molecular Biosciences, University of Newcastle upon Tyne, Framlington Place, Newcastle NE2 4HH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Musson","sequence":"additional","affiliation":[{"name":"Musculoskeletal Research Group, Clinical Medical Sciences, University of Newcastle upon Tyne, Framlington Place, Newcastle NE2 4HH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Flick-Smith","sequence":"additional","affiliation":[{"name":"Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Walker","sequence":"additional","affiliation":[{"name":"Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair","family":"McGregor","sequence":"additional","affiliation":[{"name":"Institute for Cell and Molecular Biosciences, University of Newcastle upon Tyne, Framlington Place, Newcastle NE2 4HH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather K.","family":"Lamb","sequence":"additional","affiliation":[{"name":"Institute for Cell and Molecular Biosciences, University of Newcastle upon Tyne, Framlington Place, Newcastle NE2 4HH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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