Protecting against plague: towards a next-generation vaccine

Abstract

SummaryThe causative organism of plague is the bacterium Yersinia pestis. Advances in understanding the complex pathogenesis of plague infection have led to the identification of the F1-and V-antigens as key components of a nextgeneration vaccine for plague, which have the potential to be effective against all forms of the disease. Here we review the roles of F1-and V-antigens in the context of the range of virulence mechanisms deployed by Y. pestis, in order to develop a greater understanding of the protective immune responses required to protect against plague.

Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague

“…[2][3][4] Protecting against the pneumonic form of the disease has been possible only with live attenuated strains of Y. pestis. 5 Subunit antigens of Y. pestis were identified as long ago as the mid-twentieth century, [3][4][5][6][7][8][9] but it was only with the advent of recombinant DNA technology that these could be fully exploited with consistent production of pure, stable recombinant proteins. 6,7,[10][11][12] The field of nanotechnology has growing applicability to medical biotechnology, including drug and vaccine delivery.…”

Identification of host factors required for Yersinia pestis macrophage intracellular survival and their impact on vacuole maturation, acidification and trafficking.

“…To date, there is no Federal Drug Administration (FDA) approved vaccine for Y. pestis [5,6,14,19,20,43]. There are three vaccine candidates that target LcrV, the tip of the pCD1 encoded type-three secretion system, and/or the F1 capsule, encoded by caf1 on the pMT1 plasmid.…”

“…There are three vaccine candidates that target LcrV, the tip of the pCD1 encoded type-three secretion system, and/or the F1 capsule, encoded by caf1 on the pMT1 plasmid. The first two vaccines are subunit vaccines using F1 and LcrV independently and the third is a recombinant fusion protein of rF1/LcrV [19,20,43,44]. These vaccine candidates are currently being comprehensively tested for their efficacy in both bubonic and pneumonic plague in multiple mammalian models.…”

“…These vaccine candidates are currently being comprehensively tested for their efficacy in both bubonic and pneumonic plague in multiple mammalian models. While these vaccines have previously been tested in various animal models, the robustness of lasting T and B cell responses remain undetermined (for review see [20,43,44]). …”

“…A major concern with current vaccines is isolation of F1 and pCD1 negative strains naturally form the environment [1,19,43]. These strains spontaneously lose the capsule and the T3SS.…”