PDF(Pubmed)
Abstract：
No licensed vaccine exists for the lethal plague and yersiniosis. Therefore, a combination of recombinant YopE and LcrV antigens of Yersinia pestis was evaluated for its vaccine potential in a mouse model. YopE and LcrV in formulation with alum imparted a robust humoral immune response, with isotyping profiles leaning towards the IgG1 and IgG2b subclasses. It was also observed that a significantly enhanced expression of IFN-γ, TNF-α, IL-6, IL-2, and IL-1β from the splenic cells of vaccinated mice, as well as YopE and LcrV-explicit IFN-γ eliciting T-cells. The cocktail of YopE + LcrV formulation conferred complete protection against 100 LD50Y. pestis infection, while individually, LcrV and YopE provided 80 % and 60 % protection, respectively. Similarly, the YopE + LcrV vaccinated animal group had significantly lower colony forming unit (CFU) counts in the spleen and blood compared to the groups administered with YopE or LcrV alone when challenged with Yersinia pseudotuberculosis and Yersinia enterocolitica. Histopathologic evidence reinforces these results, indicating the YopE + LcrV formulation provided superior protection against acute lung injury as early as day 3 post-challenge. In conclusion, the alum-adjuvanted YopE + LcrV is a promising vaccine formulation, eliciting a robust antibody response including a milieu of pro-inflammatory cytokines and T-cell effector functions that contribute to the protective immunity against Yersinia infections. YopE and LcrV, conserved across all three human-pathogenic Yersinia species, provide cross-protection. Therefore, our current vaccine (YopE + LcrV) targets all three pathogens: Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica. However, the efficacy should be tested in other higher mammalian models.
摘要：
没有针对致命鼠疫和耶尔森氏菌病的许可疫苗。因此,在小鼠模型中评估了鼠疫耶尔森氏菌的重组YopE和LcrV抗原的组合的疫苗潜力。YopE和LcrV与明矾的配方赋予了强大的体液免疫反应，同种型分布倾向于IgG1和IgG2b亚类。还观察到IFN-γ的表达显着增强，TNF-α,IL-6，IL-2和IL-1β来自接种小鼠的脾细胞，以及YopE和LcrV明确的IFN-γ引发T细胞。YopE+LcrV制剂的混合物赋予针对100LD50Y的完全保护。鼠疫菌感染,而单独,LcrV和YopE提供了80%和60%的保护，分别。同样，与单独使用YopE或LcrV的动物组相比,在使用假结核耶尔森氏菌和小肠结肠炎耶尔森氏菌攻击时,接种YopE+LcrV的动物组的脾脏和血液中的菌落形成单位(CFU)计数显著降低.组织病理学证据加强了这些结果，这表明YopE+LcrV制剂早在攻击后第3天就提供了针对急性肺损伤的优异保护。总之,明矾佐剂YopE+LcrV是一种有前途的疫苗制剂，引发强大的抗体反应，包括促炎细胞因子和T细胞效应子功能的环境，有助于对抗耶尔森氏菌感染的保护性免疫。YopE和LcrV,在所有三种人类致病性耶尔森氏菌物种中保守，提供交叉保护。因此,我们目前的疫苗（YopE+LcrV）针对所有三种病原体：鼠疫耶尔森氏菌，Y.假结核,和小肠结肠炎。然而,应在其他高级哺乳动物模型中测试功效。
