Nature2014-06-24 4:27 PM

可应用于疫苗研发的蛋白设计方法 Proof of principle for epitope-focused vaccine design

论文摘要 

William Schief及同事采用计算蛋白设计方法来生成人“呼吸道合胞体病毒”(RSV)疫苗的新颖候选药物。模仿一个RSV抗原决定基的结构的人造蛋白支架,被发现能在恒河猴身上诱导产生中和RSV的抗体。本文所用的蛋白设计方法(它围绕一个功能主题来设计蛋白,以稳定该主题的构形) 在疫苗研发方面有可能具有广泛应用。

Abstract 

Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Several major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus, that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for the research and development of a human respiratory syncytial virus vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets, including antigenically highly variable pathogens such as human immunodeficiency virus and influenza.

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