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含单一九聚体T细胞表位的重组疫苗对致死性巨细胞病毒感染的防护作用

Protection against lethal cytomegalovirus infection by a recombinant vaccine containing a single nonameric T-cell epitope.

作者信息

Del Val M, Schlicht H J, Volkmer H, Messerle M, Reddehase M J, Koszinowski U H

机构信息

Department of Virology, University of Ulm, Federal Republic of Germany.

出版信息

J Virol. 1991 Jul;65(7):3641-6. doi: 10.1128/JVI.65.7.3641-3646.1991.

DOI:10.1128/JVI.65.7.3641-3646.1991
PMID:1710286
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC241372/
Abstract

The regulatory immediate-early (IE) protein pp89 of murine cytomegalovirus induces CD8+ T lymphocytes that protect against lethal murine cytomegalovirus infection. The IE1 epitope is the only epitope of pp89 that is recognized by BALB/c cytolytic T lymphocytes (CTL). Using synthetic peptides, the optimal and minimal antigenic sequences of the IE1 epitope have been defined. To evaluate the predictive value of data obtained with synthetic peptides, recombinant vaccines encoding this single T-cell epitope were constructed using as a vector the hepatitis B virus core antigen encoded in recombinant vaccinia virus. In infected cells expressing the chimeric proteins, only IE1 epitope sequences that were recognized as synthetic peptides at concentrations lower than 10(-6) M were presented to CTL. Vaccination of mice with the recombinant vaccinia virus that encoded a chimeric protein carrying the optimal 9-amino-acid IE1 epitope sequence elicited CD8+ T lymphocytes with antiviral activity and, furthermore, protected against lethal disease. The results thus show for the first time that recombinant vaccines containing a single foreign nonameric CTL epitope can induce T-lymphocyte-mediated protective immunity.

摘要

小鼠巨细胞病毒的调节性立即早期(IE)蛋白pp89可诱导CD8 + T淋巴细胞,从而抵御致死性小鼠巨细胞病毒感染。IE1表位是pp89唯一能被BALB/c细胞溶解性T淋巴细胞(CTL)识别的表位。利用合成肽,已确定了IE1表位的最佳和最小抗原序列。为评估合成肽所得数据的预测价值,构建了编码该单一T细胞表位的重组疫苗,其载体为重组痘苗病毒编码的乙型肝炎病毒核心抗原。在表达嵌合蛋白的感染细胞中,只有浓度低于10(-6)M时能被识别为合成肽的IE1表位序列才能呈递给CTL。用编码携带最佳9氨基酸IE1表位序列嵌合蛋白的重组痘苗病毒给小鼠接种,可诱导具有抗病毒活性的CD8 + T淋巴细胞,进而抵御致死性疾病。因此,结果首次表明,含有单一外源九聚体CTL表位的重组疫苗可诱导T淋巴细胞介导的保护性免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398e/241372/14551cb77216/jvirol00050-0240-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398e/241372/14551cb77216/jvirol00050-0240-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398e/241372/14551cb77216/jvirol00050-0240-a.jpg

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