Polymorphism in the Yersinia LcrV Antigen Enables Immune Escape From the Protection Conferred by an LcrV-Secreting Lactococcus Lactis in a Pseudotuberculosis Mouse Model

Abstract

Yersinioses caused by <i>Yersinia pestis, Yersinia pseudotuberculosis</i>, and <i>Yersinia enterocolitica</i> are significant concerns in human and veterinary health. The link between virulence and the potent LcrV antigen has prompted the latter's selection as a major component of anti-<i>Yersinia</i> vaccines. Here, we report that (i) the group of <i>Yersinia</i> species encompassing <i>Y. pestis</i> and <i>Y. pseudotuberculosis</i> produces at least five different clades of LcrV and (ii) vaccination of mice with an LcrV-secreting <i>Lactococcus lactis</i> only protected against <i>Yersinia</i> strains producing the same LcrV clade as that of used for vaccination. By vaccinating with engineered LcrVs and challenging mice with strains producing either type of LcrV or a LcrV mutated for regions of interest, we highlight key polymorphic residues responsible for the absence of cross-protection. Our results show that an anti-LcrV-based vaccine should contain multiple LcrV clades if protection against the widest possible array of <i>Yersinia</i> strains is sought.