Data_Sheet_1_Polymorphism in the Yersinia LcrV Antigen Enables Immune Escape From the Protection Conferred by an LcrV-Secreting Lactococcus Lactis in a Pseudotuberculosis Mouse Model.pdf

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.

由鼠疫耶尔森菌（Yersinia pestis）、假结核耶尔森菌（Yersinia pseudotuberculosis）以及小肠结肠炎耶尔森菌（Yersinia enterocolitica）引发的耶尔森菌病，是人类医学与兽医健康领域的重大关切。毒力与强效LcrV抗原（LcrV）之间的紧密关联，促使该抗原被选为抗耶尔森菌疫苗的核心组分。本研究报告了两项关键发现：其一，包含鼠疫耶尔森菌与假结核耶尔森菌的耶尔森菌类群可产生至少五种不同进化枝的LcrV；其二，使用分泌LcrV的乳酸乳球菌免疫小鼠后，仅能对表达与免疫所用LcrV属于同一进化枝的耶尔森菌菌株提供保护。通过使用工程化改造的LcrV进行免疫，并以表达两类LcrV或携带目标区域突变的LcrV的菌株攻毒小鼠，本研究明确了导致交叉保护缺失的关键多态性残基。研究结果显示，若要实现对尽可能广泛的耶尔森菌菌株的广谱保护，基于抗LcrV的疫苗应涵盖多种LcrV进化枝。