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Yersinioses caused by  Yersinia pestis, Yersinia pseudotuberculosis , and  Yersinia enterocolitica  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- Yersinia  vaccines. Here, we report that (i) the group of  Yersinia  species encompassing  Y. pestis  and  Y. pseudotuberculosis  produces at least five different clades of LcrV and (ii) vaccination of mice with an LcrV-secreting  Lactococcus lactis  only protected against  Yersinia  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  Yersinia  strains is sought.

frontiers in immunology

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