Dual Immunization with SseB/Flagellin Provides Enhanced Protection against Salmonella Infection Mediated by Circulating Memory Cells
Dual Immunization with SseB/Flagellin Provides Enhanced Protection against Salmonella Infection Mediated by Circulating Memory Cells
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DOI：
10.4049/jimmunol.1601357
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发表时间：
2017-08-15
影响因子：
4.4
通讯作者：
McSorley, Stephen J.
中科院分区：
文献类型：
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作者：
Lee, Seung-Joo;Benoun, Joseph;McSorley, Stephen J.
沙门氏菌亚单位疫苗的开发一直受到阻碍的保护性沙门氏菌特异性T和B细胞的抗原靶标的详细信息的缺乏。最近的研究已经确定SseB作为一个适度的保护性抗原在易感的C57 BL/6小鼠，但保护性免疫的机制仍然不明确。在这篇文章中，我们报告说，简单地结合沙门氏菌SseB与鞭毛蛋白大大提高了保护性免疫，使免疫C57 BL/6小鼠存活长达30天后，与强毒细菌的挑战。令人惊讶的是，鞭毛蛋白的增强作用不需要鞭毛蛋白Ag靶向在次级应答或识别鞭毛蛋白的TLR 5。虽然与鞭毛蛋白共免疫不影响SseB特异性抗体应答，但它适度地增强了CD 4应答。此外，保护性免疫在循环中被有效地转移到免疫小鼠的寄生虫中，表明组织驻留记忆对于疫苗诱导的保护是不需要的。最后，保护性免疫需要宿主表达IFN-γ R，但不依赖于诱导的NO合酶表达。总之，这些数据表明沙门氏菌鞭毛蛋白具有独特的佐剂特性，可改善循环记忆提供的SseB介导的保护性免疫。
The development of a subunit Salmonella vaccine has been hindered by the absence of detailed information about antigenic targets of protective Salmonella-specific T and B cells. Recent studies have identified SseB as a modestly protective Ag in susceptible C57BL/6 mice, but the mechanism of protective immunity remains undefined. In this article, we report that simply combining Salmonella SseB with flagellin substantially enhances protective immunity, allowing immunized C57BL/6 mice to survive for up to 30 d following challenge with virulent bacteria. Surprisingly, the enhancing effect of flagellin did not require flagellin Ag targeting during secondary responses or recognition of flagellin by TLR5. Although coimmunization with flagellin did not affect SseB-specific Ab responses, it modestly boosted CD4 responses. In addition, protective immunity was effectively transferred in circulation to parabionts of immunized mice, demonstrating that tissue-resident memory is not required for vaccine-induced protection. Finally, protective immunity required host expression of IFN-gamma R but was independent of induced NO synthase expression. Taken together, these data indicate that Salmonella flagellin has unique adjuvant properties that improve SseB-mediated protective immunity provided by circulating memory.