Candidate live, attenuated Salmonella enterica serotype typhimurium vaccines with reduced fecal shedding are immunogenic and effective oral vaccines
Candidate live, attenuated Salmonella enterica serotype typhimurium vaccines with reduced fecal shedding are immunogenic and effective oral vaccines
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DOI：
10.1128/iai.01655-06
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发表时间：
2007-04-01
影响因子：
3.1
通讯作者：
Dougan, Gordon
中科院分区：
文献类型：
--
作者：
El Ghany, Moataz Abd;Jansen, Angela;Dougan, Gordon
基因操作微生物的环境脱落是阻碍新活疫苗开发的一个问题。我们已经研究了一些新型肠道沙门氏菌血清型鼠伤寒口服疫苗候选物的免疫原性，这些候选物表达破伤风毒素的C片段（TetC）组分，并在基因shdA、misL和ratB中含有额外突变的组合，这些突变有助于鼠伤寒血清型在肠道的定植。在shdA或misL或这些突变的组合中含有额外突变的鼠伤寒血清型aroA（TetC）衍生物显示经口接种小鼠粪便中疫苗株的脱落显著减少。然而，在接种疫苗小鼠的血清中检测到同等水平的抗TetC和抗沙门氏菌脂多糖免疫球蛋白G（IgG）、IgG1、IgG2a和伊加，但在对照小鼠的血清中未检测到。在所有接种疫苗的小鼠中检测到对TetC的细胞免疫应答，而不管在shd4或misL中是否存在额外的突变。此外，用含有shdA和misL的血清型鼠伤寒aroA候选疫苗免疫提供了针对血清型鼠伤寒强毒株攻击的完全保护。
Environmental shedding of genetically manipulated microorganisms is an issue impeding the development of new live vaccines. We have investigated the immunogenicity of a number of novel Salmonella enterica serotype Typhimurium oral vaccine candidates that express the fragment C (TetC) component of tetanus toxin and harbor combinations of additional mutations in genes shdA, misL, and ratB that contribute to the persistence of serotype Typhimurium's colonization of the intestine. Serotype Typhimurium aroA (TetC) derivatives harboring additional mutations in either shdA or misL or combinations of these mutations exhibited a marked decrease in shedding of the vaccine strain in the feces of orally vaccinated mice. However, equivalent levels of anti-TetC and anti-Salmonella lipopolysaccharide immunoglobulin G (IgG), IgG1, IgG2a, and IgA were detected in sera of the vaccinated but not of the control mice. Cellular immune responses to TetC were detected in all vaccinated mice, regardless of the presence of the additional mutations in shd4 or misL. Further, immunization with serotype Typhimurium aroA candidate vaccines harboring shdA and misL afforded complete protection against challenge with a virulent strain of serotype Typhimurium.