School of Fundamental Sciences , Massey University , Palmerston North 4474 , New Zealand.
Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University , Nathan , Queensland 4111 , Australia.
Biomacromolecules. 2019 Sep 9;20(9):3213-3232. doi: 10.1021/acs.biomac.9b00509. Epub 2019 Jun 10.
Spherical polyhydroxyalkanoate (PHA) inclusions are naturally self-assembled inside bacteria. These PHA beads are shell-core structures composed of a hydrophobic PHA core surrounded by proteins, such as PHA synthase (PhaC). PhaC is covalently attached and serves as an anchor protein for foreign protein vaccine candidate antigens. PHA beads displaying single and multiple antigens showed enhanced immunological properties when compared to respective soluble vaccines. This review highlights the unique design space of the PHA bead-based vaccines toward the development of safe and synthetic particulate vaccines. The PHA bead technology will be compared with chemically synthesized polyesters, such as polylactic acids, formulated to deliver vaccine antigens. The performance of PHA bead vaccine candidates to induce specific immune responses and protective immunity against bacterial and viral pathogens in animal trials will be summarized. We propose that the PHA bead technology offers a versatile vaccine platform for design and cost-effective manufacture of synthetic multivalent vaccines.
球形聚羟基烷酸酯 (PHA) 包涵体在细菌内自然自组装。这些 PHA 珠粒是由疏水 PHA 核心和周围的蛋白质(如 PHA 合酶 (PhaC))组成的壳核结构。PhaC 通过共价键连接并作为外来蛋白疫苗候选抗原的锚定蛋白。与相应的可溶性疫苗相比,展示单个和多个抗原的 PHA 珠粒显示出增强的免疫特性。本综述强调了基于 PHA 珠粒的疫苗在开发安全和合成颗粒疫苗方面的独特设计空间。PHA 珠粒技术将与化学合成的聚酯(如聚乳酸)进行比较,这些聚酯被设计用于输送疫苗抗原。将总结 PHA 珠粒疫苗候选物在动物试验中诱导针对细菌和病毒病原体的特异性免疫应答和保护免疫的性能。我们提出,PHA 珠粒技术为设计和经济高效地制造合成多价疫苗提供了一种多功能疫苗平台。