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首页> 外文期刊>Infection and immunity >Superior Protective Immunity against Murine Listeriosis by Combined Vaccination with CpG DNA and Recombinant Salmonella enterica Serovar Typhimurium
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Superior Protective Immunity against Murine Listeriosis by Combined Vaccination with CpG DNA and Recombinant Salmonella enterica Serovar Typhimurium

机译:通过联合接种CpG DNA和重组肠炎沙门氏菌血清鼠伤寒疫苗对鼠李斯特菌病提供超强保护性免疫

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Preexisting antivector immunity can severely compromise the ability of Salmonella enterica serovar Typhimurium live vaccines to induce protective CD8 T-cell frequencies after type III secretion system-mediated heterologous protein translocation in orally immunized mice. To circumvent this problem, we injected CpG DNA admixed to the immunodominant p60217-225 peptide from Listeria monocytogenes subcutaneously into BALB/c mice and coadministered a p60-translocating Salmonella strain by the orogastric route. The distribution of tetramer-positive p60217-225-specific effector and memory CD8 T cells was analyzed by costaining of lymphocytes with CD62L and CD127. In contrast to the single oral application of recombinant Salmonella or single immunization with CpG and p60, in the spleens from mice immunized with a combination of both vaccine types a significantly higher level of p60-specific CD8 T cells with a predominance of the effector memory T-cell subset was detected. In vivo protection studies revealed that this CD8 T-cell population conferred sterile protective immunity against a lethal infection with L. monocytogenes. However, p60-specific central memory CD8 T cells induced by single vaccination with CpG and p60 were not able confer effective protection against rapidly replicating intracellular Listeria. In conclusion, we provide compelling evidence that the combination of Salmonella type III-mediated antigen delivery and CpG immunization is an attractive novel vaccination strategy to modulate CD8 differentiation patterns toward distinct antigen-specific T-cell subsets with favorable protective capacities.
机译:在口服免疫的小鼠中,III型分泌系统介导的异源蛋白易位后,预先存在的抗载体免疫力会严重损害肠沙门氏菌血清型鼠伤寒活疫苗诱导CD8 T细胞保护性频率的能力。为了解决这个问题,我们将与单核细胞增生性李斯特菌的免疫优势p60 217-225 肽混合的CpG DNA皮下注射到BALB / c小鼠体内,并共同施用了一个转运p60的沙门氏菌通过口胃途径传播。通过与CD62L和CD127淋巴细胞共染色,分析四聚体阳性的p60 217-225 特异性效应子和记忆CD8 T细胞的分布。与单次口服重组沙门氏菌或用CpG和p60进行单次免疫相比,在两种疫苗组合免疫后小鼠的脾脏中,p60特异性CD8 T细胞和检测到效应记忆T细胞亚群占优势。体内保护研究表明,该CD8 T细胞群具有针对 L致死性感染的无菌保护性免疫力。单核细胞增生。然而,通过单次接种CpG和p60诱导的p60特异性中央记忆CD8 T细胞不能有效抵抗快速复制的细胞内 Listeria 。总之,我们提供了令人信服的证据,表明沙门氏菌 III型介导的抗原递送和CpG免疫相结合是一种有吸引力的新型疫苗接种策略,可将CD8分化模式调节为具有独特抗原的不同抗原特异性T细胞亚群保护能力。

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