Relationship Between Virulence and Immunity as Revealed in Recent Studies of the Fl Capsule of Yersinia pestis

Abstract

Yersinia pestis, the causative agent of plague, possesses multiple virulence determinants encoded on its three plasmids and on its chromosome. We evaluated the role of the protein capsule FI in virulence and immunity against plague. Strains lacking Fl, either those that are naturally occurring or those with genetically defined nonpolar mutations in the structural gene, retained their virulence for mice and nonhuman primates. However, both active immunization with FI, from either a recombinant vector or Y. pestis, and passive immunization with FI monoclonal antibody protected mice from experimental infection with wild-type Fl-positive organisms. These results suggest that protective immunogens like Fl need not be essential for virulence. The rare isolation of virulent Fl-negative organisms from Fl-immunized animals infected with Fl-positive strains supports this conclusion and also suggests that, in addition to FI, an optimal vaccine against plague should include essential virulence factors as immunogens.