Identification of murine CD8 T cell epitopes in codon-optimized SARS-associated coronavirus spike protein.

Identification of murine CD8 T cell epitopes in codon-optimized SARS-associated coronavirus spike protein.
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DOI:
10.1016/j.virol.2005.01.050
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发表时间:
2005-04-25
期刊:
影响因子:
3.7
通讯作者:
Wilson JM
Wilson JM
中科院分区:
医学3区
文献类型:
--
作者:
Zhi Y;Kobinger GP;Jordan H;Suchma K;Weiss SR;Shen H;Schumer G;Gao G;Boyer JL;Crystal RG;Wilson JM

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严重急性呼吸综合征(SARS)的病原体已被确定为一种新型冠状病毒——SARS相关冠状病毒(SARS- cov)。在相应的动物模型中,CD8 T细胞在控制其他冠状病毒引起的疾病和介导疫苗诱导的保护性免疫中发挥重要作用。刺突蛋白是sars冠状病毒的主要表面抗原,是疫苗设计中最重要的候选抗原之一。利用重叠肽鉴定编码密码子优化的SARS-CoV刺突蛋白的载体免疫小鼠的主要组织相容性复合体i类限制性表位。CD8 t细胞应答定位到两个h -2b限制性表位(S436-443和S525-532)和一个h -2d限制性表位(S366-374)。这些表位的鉴定将有助于在小鼠SARS-CoV感染模型中评估疫苗策略。此外,密码子和启动子优化可以大大提高刺突蛋白在人类和猿猴腺病毒疫苗携带者中复制缺陷的整体免疫原性。优化后的编码刺突的重组腺病毒疫苗载体可在小鼠体内产生强大的抗原特异性细胞免疫,可能用于控制SARS-CoV感染。
The causative agent of severe acute respiratory syndrome (SARS) has been identified as a new type of coronavirus, SARS-associated coronavirus (SARS-CoV). CD8 T cells play an important role in controlling diseases caused by other coronaviruses and in mediating vaccine-induced protective immunity in corresponding animal models. The spike protein, a main surface antigen of SARS-CoV, is one of the most important antigen candidates for vaccine design. Overlapping peptides were used to identify major histocompatibility complex class I-restricted epitopes in mice immunized with vectors encoding codon-optimized SARS-CoV spike protein. CD8 T-cell responses were mapped to two H-2b-restricted epitopes (S436–443 and S525–532) and one H-2d-restricted epitope (S366–374). The identification of these epitopes will facilitate the evaluation of vaccine strategies in murine models of SARS-CoV infection. Furthermore, codon and promoter optimizations can greatly enhance the overall immunogenicity of spike protein in the context of replication-defective human and simian adenoviral vaccine carriers. The optimized recombinant adenoviral vaccine vectors encoding spike can generate robust antigen-specific cellular immunity in mice and may potentially be useful for control of SARS-CoV infection.
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