A Synthetic Biology Approach to Engineering Protein Assemblies for use in Vaccine Design

生物纳米技术是一门新兴的科学，旨在利用生物自组装的原理，结合结构和生化知识，设计纳米级大分子结构，并将其应用于医学和相关领域。近年来，利用异源的、非天然的融合蛋白与工程连接体，能够形成大的、稳定的、多聚体的组装体方面取得了进展。这种结构的发展为设计规则组装提供了令人兴奋的可能性，这些组装可以用作展示感染性细菌抗原的多个拷贝的平台。然后，这些组合物将以类似于病毒样颗粒的方式，有效地引发保护性免疫反应，病毒样颗粒已被广泛用作临床疫苗。要设计这种结构，表达和分离它，验证其组装并证明其作为疫苗的有效性，需要一系列的技能，从基于计算和合成生物学的设计，蛋白质生物化学，结构生物学和免疫学。这一多学科项目将研究这种新方法开发脑膜炎球菌性脑膜炎疫苗的潜力。这是发展中国家和发达国家的一种严重疾病；控制的努力只取得了有限的成功，部分原因是血清B组生物的表面蛋白抗原与致病细菌脑膜炎奈瑟菌有很大的差异。将设计、生产和测试含有脑膜炎抗原的设计人工组装物，以确定其刺激产生能够杀死脑膜炎奈瑟菌的抗体的能力。最终，这种方法可能会导致一种开发疫苗的新方法。Callaghan等人（2011）《感染》。[3]李春华，李春华，李春华，等。化学。Saleem et al. (2013) Plos One. 8 doi:e5674610.1371King et al. (2014) Nature 510, 103-108

The emerging science of Bionanotechnology aims to use the principles of biological self-assembly, combined with structural and biochemical knowledge, to engineer nanoscale macromolecular structures with applications in medicine and related fields. Advances have been made recently in using heterologous, non-natural fusion proteins with engineered linkers that are capable of forming large, stable, multimeric assemblies. The development of such structures raises exciting possibilities for the design of regular assemblies which could be used as platforms for the display of multiple copies of antigens from an infectious bacterium. These assemblies would then be effective at eliciting a protective immune response, in a similar fashion to virus-like particles, which are already in widespread clinical use as vaccines. To design such a structure, express and isolate it, verify the assembly and demonstrate its effectiveness as a vaccine requires a range of skills, from computation and synthetic biology-based design, protein biochemistry, structural biology and immunology. This multidisciplinary project will examine the potential of this novel approach to develop a vaccine against meningococcal meningitis. This is a serious disease in developing and developed countries; attempts at control have met with only limited success, partly due to the considerable variation in surface protein antigens from serogroup B organisms from the causative bacterium, Neisseria meningitidis. Designed artificial assemblies, with incorporated meningitis antigens, will be designed, produced and tested for their ability to stimulate the production of antibodies which are capable of killing N. meningitidis. Ultimately, this approach could lead to a new way of developing vaccines. Callaghan et al. (2011) Infect. Immun. 79, 2810-2818Lai et al. (2013) J. Am. Chem. Soc. 135, 7738-7743 Saleem et al. (2013) Plos One. 8 doi:e5674610.1371King et al. (2014) Nature 510, 103-108