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首页> 外文期刊>Infection and immunity >A sopB Deletion Mutation Enhances the Immunogenicity and Protective Efficacy of a Heterologous Antigen Delivered by Live Attenuated Salmonella enterica Vaccines
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A sopB Deletion Mutation Enhances the Immunogenicity and Protective Efficacy of a Heterologous Antigen Delivered by Live Attenuated Salmonella enterica Vaccines

机译：sopB缺失突变增强了由减毒活沙门氏菌疫苗提供的异源抗原的免疫原性和保护功效。

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SopB is a virulence factor of Salmonella encoded by SPI-5. Salmonella sopB deletion mutants are impaired in their ability to cause local inflammatory responses and fluid secretion into the intestinal lumen and also can enhance the immunogenicity of a vectored antigen. In this study, we evaluated the effects on immunogenicity and the efficacy of a sopB deletion mutation on two Salmonella enterica serovar Typhimurium vaccine strains with different attenuating mutations expressing a highly antigenic α-helical region of the Streptococcus pneumoniae surface protein PspA from an Asd+-balanced lethal plasmid. After oral administration to mice, the two pairs of strains induced high levels of serum antibodies specific for PspA as well as to Salmonella antigens. The levels of antigen-specific serum immunoglobulin G (IgG) and mucosal IgA were higher in mice immunized with sopB mutants. Enzyme-linked immunospot assay results indicated that the spleen cells from mice immunized with a sopB mutant showed higher interleukin-4 and gamma interferon secretion levels than did the mice immunized with the isogenic sopB+ strain. The sopB mutants also induced higher numbers of CD4+ CD44hi CD62Lhi and CD8+ CD44hi CD62Lhi central memory T cells. Eight weeks after primary oral immunization, mice were challenged with 100 50% lethal doses of virulent S. pneumoniae WU2. Immunization with either of the sopB mutant strains led to increased levels of protection compared to that with the isogenic sopB+ parent. Together, these results demonstrate that the deletion of sopB leads to an overall enhancement of the immunogenicity and efficacy of recombinant attenuated Salmonella vaccine strains.
机译：SopB是SPI-5编码的沙门氏菌的毒力因子。沙门氏菌sopB 缺失突变体引起局部炎症反应和向肠腔内分泌液体的能力受到损害，还可以增强载体抗原的免疫原性。在这项研究中，我们评估了对两种表达高抗原性α-减毒突变的 Salmonella enterica 血清型鼠伤寒沙门氏菌疫苗株的免疫原性和 sopB 缺失突变的影响。 Asd + 平衡致死质粒中肺炎链球菌表面蛋白PspA的螺旋区域。对小鼠口服给药后，这两对菌株诱导了高水平的PspA和 Salmonella 抗原特异的血清抗体。用 sopB 突变体免疫的小鼠中的抗原特异性血清免疫球蛋白G（IgG）和粘膜IgA水平较高。酶联免疫斑点法检测结果表明，用 sopB 突变体免疫的小鼠的脾细胞显示出比用等基因 sopB + 株。 sopB 突变体还诱导了更高数量的CD4 + CD44 hi CD62L hi 和CD8 + CD44 hi CD62L hi 中央记忆T细胞。初次口服免疫后八周，用100 50％致死剂量的有毒 S攻击小鼠。肺炎 WU2。与同基因的 sopB + 亲本相比，使用 sopB 突变株中的任一种进行免疫均可提高保护水平。总之，这些结果表明， sopB 的缺失导致重组减毒的 Salmonella 疫苗株的免疫原性和功效的全面增强。

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