CD8+ T cell adjuvant effects of Salmonella FliCd flagellin in live vaccine vectors or as purified protein
CD8+ T cell adjuvant effects of Salmonella FliCd flagellin in live vaccine vectors or as purified protein
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DOI：
10.1016/j.vaccine.2009.11.003
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发表时间：
2010-02-03
期刊：
影响因子：
5.5
通讯作者：
Ferreira, Luis C. S.
中科院分区：
文献类型：
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作者：
Braga, Catarina J. M.;Massis, Liliana M.;Ferreira, Luis C. S.
沙门氏菌鞭毛蛋白是鞭毛结构亚基，作为一种疫苗佐剂，具有增强可溶性蛋白或肽的免疫原性，可激活抗体和细胞免疫反应。在本研究中，我们以9-mer （SYVPSAEQI）合成的来自约氏疟原虫环孢子子(G)蛋白的H2(d)限制性CD8(+) T细胞特异性表位（CS280-288）为模型，对肠沙门氏菌FliCd鞭毛蛋白作为T细胞疫苗佐剂进行了评价。在两种不同的条件下确定了FliCd的佐剂效果：(i)作为重组鞭毛，通过口服表达在中心高变结构域融合的目标CS280-288肽的活S. Dublin疫苗菌株表达；（ii）作为纯化蛋白，在脱细胞疫苗中将鞭毛蛋白作为融合或与目标CS280-288肽混合的重组蛋白施用于小鼠。结果表明，将表达CS280-288表位的S. Dublin疫苗株口服接种BALB/c小鼠，可引发CS280-288特异性细胞毒CD8(+) T细胞。相比之下，用纯化的FliCd与CS280-288肽混合并在较小程度上与靶肽融合免疫的小鼠，在不需要外源加强免疫的情况下，产生了特异性的细胞毒性CD8(+) T细胞反应。鞭毛蛋白对CD8(+) T细胞的辅助作用，无论是否与靶肽融合，都与CD11c（+）树突状细胞的体内活化相关。综上所述，目前的结果表明，鞭毛沙门氏菌是一种灵活的佐剂，当通过不同的途径或疫苗配方给药时，可以诱导适应性免疫反应。2009爱思唯尔有限公司版权所有。
Salmonella flagellin, the flagellum structural subunit, has received particular interest as a vaccine adjuvant conferring enhanced immunogenity to soluble proteins or peptides, both for activation of antibody and cellular immune responses. In the present study, we evaluated the Salmonella enterica FliCd flagellin as a T cell vaccine adjuvant using as model the 9-mer (SYVPSAEQI) synthetic H2(d)-restricted CD8(+) T cell-specific epitope (CS280-288) derived from the Plasmodium yoelii circumsporozoite (G) protein. The FliCd adjuvant effects were determined under two different conditions: (i) as recombinant flagella, expressed by orally delivered live S. Dublin vaccine strains expressing the target CS280-288 peptide fused at the central hypervariable domain, and (ii) as purified protein in acellular vaccines in which flagellin was administered to mice either as a recombinant protein fused or admixed with the target CS280-288 peptide. The results showed that CS280-288-specific cytotoxic CD8(+) T cells were primed when BALB/c mice were orally inoculated with the expressing the CS280-288 epitope S. Dublin vaccine strain. In contrast, mice immunized with purified FliCd admixed with the CS280-288 peptide and, to a lesser extent, fused with the target peptide developed specific cytotoxic CD8(+) T cell responses without the need of a heterologous booster immunization. The CD8(+) T cell adjuvant effects of flagellin, either fused or not with the target peptide, correlated with the in vivo activation of CD11c(+) dendritic cells. Taken together, the present results demonstrate that Salmonella flagellins are flexible adjuvant and induce adaptative immune responses when administered by different routes or vaccine formulations. (C) 2009 Elsevier Ltd. All rights reserved.