Plague Research Today is a free monthly online journal that collates and summarizes the latest research about Plague, including details on bubonic plague, yersinia pestis, infection, types, treatment.

Immunogenicity of a Yersinia pestis vaccine antigen monomerized by circular permutation.

Chalton DA, Musson JA, Flick-Smith H, Walker N, McGregor A, Lamb HK, Williamson ED, Miller J, Robinson JH, Lakey JH

Institute for Cell and Molecular Biosciences, University of Newcastle upon Tyne, Framlington Place, Newcastle NE2 4HH, United Kingdom.

Caf1, a chaperone-usher protein from Yersinia pestis, is a major protective antigen in the development of subunit vaccines against plague. However, recombinant Caf1 forms polymers of indeterminate size. 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 Y. pestis in vivo. In C57BL/6 mice, for which the major H-2(b)-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 H-2(d)-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.

Published 22 November 2006 in Infect Immun, 74(12): 6624-31.
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