A sopB Deletion Mutation Enhances the Immunogenicity and Protective Efficacy of a Heterologous Antigen Delivered by Live Attenuated Salmonella enterica Vaccines
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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sopB 缺失突变增强了减毒肠沙门氏菌疫苗提供的异源抗原的免疫原性和保护功效
DOI：
10.1128/iai.00720-08
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发表时间：
2008-11-01
影响因子：
3.1
通讯作者：
Curtiss, Roy, III
中科院分区：
文献类型：
--
作者：
Li, Yuhua;Wang, Shifeng;Curtiss, Roy, III
SopB 是由 SPI-5 编码的沙门氏菌毒力因子。沙门氏菌 sopB 缺失突变体引起局部炎症反应和液体分泌到肠腔的能力受损，并且还可以增强载体抗原的免疫原性。在本研究中，我们评估了 sopB 缺失突变对两种鼠伤寒沙门氏菌疫苗株的免疫原性和功效的影响，这两种疫苗株具有不同的减毒突变，表达来自 Asd(+) 平衡致死质粒的肺炎链球菌表面蛋白 PspA 的高抗原性 α 螺旋区域。给小鼠口服后，两对菌株诱导产生高水平的 PspA 和沙门氏菌抗原特异性血清抗体。在用 sopB 突变体免疫的小鼠中，抗原特异性血清免疫球蛋白 G (IgG) 和粘膜 IgA 的水平较高。酶联免疫斑点测定结果表明，用sopB突变体免疫的小鼠的脾细胞比用同基因sopB(+)菌株免疫的小鼠表现出更高的白细胞介素4和γ干扰素分泌水平。 sopB突变体还诱导了更多数量的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 份 50% 致死剂量的强毒力肺炎链球菌 WU2 攻击小鼠。与同基因 sopB(+) 亲本相比，使用任一 sopB 突变株进行免疫都会导致保护水平增加。总之，这些结果表明，sopB 的缺失导致重组减毒沙门氏菌疫苗株的免疫原性和功效全面增强。
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 alpha-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(+) CD44(hi) CD62L(hi) and CD8(+) CD44(hi) CD62L(hi) 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.