SALMONELLA-TYPHIMURIUM AROA MUTANTS AS CARRIERS OF THE ESCHERICHIA-COLI HEAT-LABILE ENTEROTOXIN-B SUBUNIT TO THE MURINE SECRETORY AND SYSTEMIC IMMUNE-SYSTEMS
SALMONELLA-TYPHIMURIUM AROA MUTANTS AS CARRIERS OF THE ESCHERICHIA-COLI HEAT-LABILE ENTEROTOXIN-B SUBUNIT TO THE MURINE SECRETORY AND SYSTEMIC IMMUNE-SYSTEMS
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DOI：
10.1016/0882-4010(87)90022-2
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发表时间：
1987-03-01
影响因子：
3.8
通讯作者：
DOUGAN, G
中科院分区：
文献类型：
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作者：
MASKELL, DJ;SWEENEY, KJ;DOUGAN, G
我们研究了鼠伤寒沙门氏菌疫苗向小鼠的全身和分泌免疫系统递送异源抗原的能力，同时保留其对沙门氏菌病的免疫原性。S.用aroA无毒突变体鼠伤寒沙门氏菌SL 3261或携带编码大肠杆菌LT-B基因的质粒pBRD 026、pBR 322衍生物的SL 3261经口免疫BALB/c小鼠。两种免疫菌株均侵入小鼠的单核吞噬细胞系统，缓慢生长直至感染后约14天，然后迅速清除。到第42天，在肝脏、脾脏、肠系膜淋巴结或派伊尔集合淋巴结中未检测到沙门氏菌。用任一菌株免疫小鼠，并在清除免疫生物体后数周用强毒亲本菌株SL 1344口服攻击，可保护小鼠免受致死性S.鼠伤寒感染感染SL 3261（pBRD 026）的小鼠在感染后14天在血清和肠道样品中均产生了显著水平的IgG和伊加抗LT-B抗体。在体外Vero细胞试验中，血清中和LT的作用。因此，S.鼠伤寒沙门氏菌可以将来自不同肠道病原体的异源抗原递送到鼠全身和分泌免疫系统，而不改变它们对沙门氏菌病的功效。
We investigated the ability of Salmonella typhimurium vaccines to deliver heterologous antigens to the systemic and secretory immune systems of the mouse, while retaining their immunogenicity against salmonellosis. S. typhimurium SL3261, an avirulent aroA mutant, or SL3261 carrying plasmid pBRD026, pBR322 derivative encoding the gene for Escherichia coli LT-B were used to immunize BALB/c mice orally. Both immunizing strains invaded the mononuclear phagocyte system of the mice, grew slowly until approximately day 14 post-infection, and then were rapidly cleared. No salmonellae were detected in livers, spleens, mesenteric lymph nodes or Peyer''s patches by day 42. Mice immunized with either strain and challenged orally with the virulent parent strain, SL1344, several weeks after clearing the immunizing organism, were protected against the lethal S. typhimurium infection. Mice infected with SL3261 (pBRD026) developed substantial levels of IgG and IgA anti-LT-B antibodies 14 days post-infection in both serum and gut samples. The sera neutralized the effects of LT in an in vitro Vero cell assay. Thus, aroA mutants of S. typhimurium can deliver a heterologous antigen from a different enteric pathogen to the murine systemic and secretory immune systems without altering their efficacy against salmonellosis.