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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structure-based approach to rationally design a chimeric protein for an effective vaccine against Group B Streptococcus infections
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Structure-based approach to rationally design a chimeric protein for an effective vaccine against Group B Streptococcus infections

机译:基于结构的方法合理设计嵌合蛋白,用于抗B组链球菌感染的有效疫苗

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摘要

Structural vaccinology is an emerging strategy for the rational design of vaccine candidates. We successfully applied structural vaccinology to design a fully synthetic protein with multivalent protection activity. In Group B Streptococcus, cell-surface pili have aroused great interest because of their direct roles in virulence and importance as protective antigens. The backbone subunit of type 2a pilus (BP-2a) is present in six immunogenically different but structurally similar variants. We determined the 3D structure of one of the variants, and experimentally demonstrated that protective antibodies specifically recognize one of the four domains that comprise the protein. We therefore constructed a synthetic protein constituted by the protective domain of each one of the six variants and showed that the chimeric protein protects mice against the challenge with all of the type 2a pilus-carrying strains. This work demonstrates the power of structural vaccinology and will facilitate the development of an optimized, broadly protective pilus-based vaccine against Group B Streptococcus by combining the uniquely generated chimeric protein with protective pilin sub-units from two other previously identified pilus types. In addition, this work describes a template procedure that can be followed to develop vaccines against other bacterial pathogens.
机译:结构疫苗学是合理设计候选疫苗的新兴策略。我们成功地应用结构疫苗学设计了具有多价保护活性的完全合成的蛋白质。在B组链球菌中,细胞表面菌毛引起了极大的兴趣,因为它们在毒力中的直接作用和作为保护性抗原的重要性。 2a型菌毛的主链亚基(BP-2a)存在六个免疫原性不同但结构相似的变体。我们确定了变体之一的3D结构,并通过实验证明保护性抗体特异性识别包含该蛋白质的四个域之一。因此,我们构建了由六个变体中每个变体的保护结构域构成的合成蛋白,并表明该嵌合蛋白可保护小鼠免受所有2a型菌毛携带株的攻击。这项工作证明了结构疫苗学的力量,并将独特产生的嵌合蛋白与来自其他两种先前鉴定的菌毛类型的保护性菌毛蛋白亚基结合在一起,将有助于开发针对B组链球菌的优化的,具有广泛保护性的菌毛基疫苗。此外,这项工作描述了一种模板程序,可以遵循该程序开发针对其他细菌病原体的疫苗。

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