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Effect of deletion of gene cluster involved in synthesis of Enterobacterial common antigen on virulence and immunogenicity of live attenuated Salmonella vaccine when delivering heterologous Streptococcus pneumoniae antigen PspA.
BMC Microbiology ( IF 4.0 ) Pub Date : 2020-06-08 , DOI: 10.1186/s12866-020-01837-0
Qing Liu 1, 2 , Xuegang Shen 1 , Xiaoping Bian 1 , Qingke Kong 1
Affiliation  

Enterobacterial common antigen (ECA) is a family-specific surface antigen shared by all members of the Enterobacteriaceae family. Previous studies showed that the loss of ECA results in Salmonella attenuation, indicating its usefulness as a vaccine candidate for Salmonella infection, but no studies have shown whether the mutation resulting from the deletion of the ECA operon in conjunction with other mutations could be used as an antigen vehicle for heterologous protein antigen delivery. In this study, we introduced a nonpolar, defined ECA operon deletion into wild-type S. Typhimurium χ3761 and an attenuated vaccine strain χ9241, obtaining two isogenic ECA operon mutants, namely, χ12357 and χ12358, respectively. A number of in vitro and in vivo properties of the mutants were analyzed. We found that the loss of ECA did not affect the growth, lipopolysaccharide (LPS) production and motility of S. Typhimurium wild type strain χ3761 and its attenuated vaccine strain χ9241 but significantly affected the virulence when administered orally to BALB/c mice. Furthermore, the effects of the ECA mutation on the immunogenicity of a recombinant S. Typhimurium vaccine strain χ9241 when delivering the pneumococcal antigen PspA were determined. The result showed that the total anti-PspA IgG level of χ12358 (pYA4088) was slightly lower than that of χ9241 (pYA4088), but the protection rate was not compromised. ECA affects virulence and benefits the Th2 immunity of Salmonella Typhimurium, therefore, it is feasible to use a reversible ECA mutant mode to design future Salmonella vaccine strains for heterologous protective antigens.

中文翻译:


涉及肠杆菌共同抗原合成的基因簇的缺失对沙门氏菌减毒活疫苗在递送异源肺炎链球菌抗原PspA时的毒力和免疫原性的影响。



肠杆菌共同抗原(ECA)是肠杆菌科所有成员共有的家族特异性表面抗原。先前的研究表明,ECA 的缺失会导致沙门氏菌减毒,这表明其作为沙门氏菌感染候选疫苗的有用性,但没有研究表明 ECA 操纵子缺失与其他突变结合产生的突变是否可以用作沙门氏菌感染的候选疫苗。用于异源蛋白质抗原递送的抗原载体。在本研究中,我们将非极性、明确的ECA操纵子缺失引入野生型鼠伤寒沙门氏菌χ3761和减毒疫苗株χ9241中,获得两个同基因ECA操纵子突变体,分别为χ12357和χ12358。分析了突变体的许多体外和体内特性。我们发现ECA的缺失并不影响鼠伤寒沙门氏菌野生型菌株χ3761及其减毒疫苗菌株χ9241的生长、脂多糖(LPS)产生和运动性,但显着影响BALB/c小鼠口服给药时的毒力。此外,还确定了ECA突变对重组​​鼠伤寒沙门氏菌疫苗株χ9241在递送肺炎球菌抗原PspA时的免疫原性的影响。结果显示,χ12358(pYA4088)的总抗PspA IgG水平略低于χ9241(pYA4088),但保护率并未受到影响。 ECA影响鼠伤寒沙门氏菌的毒力并有利于Th2免疫,因此利用可逆的ECA突变模式设计未来的异源保护性抗原沙门氏菌疫苗株是可行的。
更新日期:2020-06-08
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