Multi high-throughput approach for highly selective identification of vaccine candidates: the Group A Streptococcus case.
Multi high-throughput approach for highly selective identification of vaccine candidates: the Group A Streptococcus case.
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DOI：
10.1074/mcp.m111.015693
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发表时间：
2012-06
期刊：
影响因子：
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通讯作者：
Grandi G
中科院分区：
文献类型：
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作者：
Bensi G;Mora M;Tuscano G;Biagini M;Chiarot E;Bombaci M;Capo S;Falugi F;Manetti AG;Donato P;Swennen E;Gallotta M;Garibaldi M;Pinto V;Chiappini N;Musser JM;Janulczyk R;Mariani M;Scarselli M;Telford JL;Grifantini R;Norais N;Margarit I;Grandi G
我们提出了一种实验策略，高度准确的选择候选细菌疫苗，而不使用体外和/或体内保护试验。从观察到有效疫苗由保守的、表面结合的和/或分泌的组分构成开始，该策略考虑并行应用三种高通量技术，即基于质谱的蛋白质组学、蛋白质阵列和流式细胞术分析，以鉴定这类蛋白质，并且基于由所有三种技术鉴定的抗原是保护性抗原的假设。当我们对A组链球菌测试这种策略时，我们总共选择了40种蛋白质，其中只有6种通过所有三种方法鉴定。当在小鼠模型中测试这40种蛋白质时，发现只有6种具有保护作用，其中5种属于这三种技术共有的抗原组。最后，三种保护性抗原的组合赋予了针对四种不同A组链球菌菌株的广泛保护。这种方法可以作为细菌疫苗发现的加速和高度准确的途径而得到普遍应用。
We propose an experimental strategy for highly accurate selection of candidates for bacterial vaccines without using in vitro and/or in vivo protection assays. Starting from the observation that efficacious vaccines are constituted by conserved, surface-associated and/or secreted components, the strategy contemplates the parallel application of three high throughput technologies, i.e. mass spectrometry-based proteomics, protein array, and flow-cytometry analysis, to identify this category of proteins, and is based on the assumption that the antigens identified by all three technologies are the protective ones. When we tested this strategy for Group A Streptococcus, we selected a total of 40 proteins, of which only six identified by all three approaches. When the 40 proteins were tested in a mouse model, only six were found to be protective and five of these belonged to the group of antigens in common to the three technologies. Finally, a combination of three protective antigens conferred broad protection against a panel of four different Group A Streptococcus strains. This approach may find general application as an accelerated and highly accurate path to bacterial vaccine discovery.