SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation
SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation
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DOI：
10.1111/j.0001-2815.2004.00221.x
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发表时间：
2004-05-01
期刊：
影响因子：
--
通讯作者：
Buus, S
中科院分区：
文献类型：
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作者：
Sylvester-Hvid, C;Nielsen, M;Buus, S
有效的严重急性呼吸道综合征（SARS）疫苗可能包括能够诱导特异性细胞毒性T淋巴细胞（CTL）反应的成分。这种反应的特异性由SARS衍生肽表位的人类白细胞抗原（HLA）限制性呈递控制。免疫系统如何处理蛋白抗原的精确知识将允许从基因组/蛋白质组序列信息直接鉴定此类线性序列（Lauemoller等人，Rev Immunogenet 2001：2：477-91）。后者是最近在分离致病性冠状病毒（SARS-CoV）并进行全长测序时建立的（Marra et al.，Science 2003：300：1399404）。在这里，我们结合先进的生物信息学和高通量免疫学进行HLA超型，全基因组扫描SARS特异性CTL表位。扫描包括全部九种人类HLA超型，总共覆盖所有主要人群的所有个体的>99%（Sette & Sidney，Immunogenetics 1999：50：201-12）。对于每个HLA超型，我们选择了15个最佳候选者用于生化结合试验。在这个时候（大约2 - 6个月后的基因组建立），我们已经测试了大多数的HLA超型，并确定了近100个潜在的候选疫苗。这些应在SARS幸存者中进一步验证，并用于疫苗配制。我们认为，免疫生物信息学可能成为一个快速和有价值的工具，在合理的疫苗设计。
An effective Severe Acute Respiratory Syndrome (SARS) vaccine is likely to include components that can induce specific cytotoxic T-lymphocyte (CTL) responses. The specificities of such responses are governed by human leukocyte antigen (HLA)-restricted presentation of SARS-derived peptide epitopes. Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly, from genomic/proteomic sequence information (Lauemoller et al., Rev Immunogenet 2001: 2: 477-91). The latter was recently established when a causative coronavirus (SARS-CoV) was isolated and full-length sequenced (Marra et al., Science 2003: 300: 1399404). Here, we have combined advanced bioinformatics and high-throughput immunology to perform an HLA supertype-, genome-wide scan for SARS-specific CTL epitopes. The scan includes all nine human HLA supertypes in total covering >99% of all individuals of all major human populations (Sette & Sidney, Immunogenetics 1999: 50: 201-12). For each HLA supertype, we have selected the 15 top candidates for test in biochemical binding assays. At this time (approximately 2 6 months after the genome was established), we have tested the majority of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design.