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

Front Immunol. 2019 Aug 2;10:1830. doi: 10.3389/fimmu.2019.01830. eCollection 2019.


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.

Keywords: Lactoccus lactis; LcrV; Yersinia pestis; immune escape; plague; polymorphism; probiotic; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / immunology
  • Antigens, Bacterial / immunology*
  • Bacterial Vaccines / immunology*
  • Cross Protection / immunology
  • Disease Models, Animal
  • Female
  • Lactococcus lactis / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Pore Forming Cytotoxic Proteins / immunology*
  • Vaccination / methods
  • Virulence / immunology
  • Yersinia Infections / immunology
  • Yersinia pestis / immunology*
  • Yersinia pseudotuberculosis / immunology*


  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Vaccines
  • LcrV protein, Yersinia
  • Pore Forming Cytotoxic Proteins