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

Catherine Daniel (1) , Amélie Dewitte (1) , Sabine Poiret (1) , Michaël Marceau (1) , Michel Simonet (1) , Laure Marceau (1) , Guillaume Descombes (1) , Denise Boutillier (1) , Nadia Bennaceur (1) , Sébastien Bontemps­-Gallo (1) , Nadine Lemaître (1) , Florent Sebbane (1)

1 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204

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.

Mots clés: plague; Yersinia pestis; vaccine; LcrV; immune escape; polymorphism; probiotic; Lactoccus lactis

Domaines: Sciences du Vivant [q-bio]

Catherine Daniel, Amélie Dewitte, Sabine Poiret, Michaël Marceau, Michel Simonet, et al.. Polymorphism in the Yersinia LcrV Antigen Enables Immune Escape From the Protection Conferred by an LcrV-Secreting Lactococcus Lactis in a Pseudotuberculosis Mouse Model. Frontiers in Immunology, 2019, 10, pp.1830. ⟨10.3389/fimmu.2019.01830⟩. ⟨pasteur-02946846⟩