Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.
Finlay Vaccine Institute, La Havana, Cuba.
Sci Rep. 2018 Jan 30;8(1):1888. doi: 10.1038/s41598-018-20205-7.
The efficacy of protein and carbohydrate antigens as vaccines can be improved via particulate delivery strategies. Here, protein and carbohydrate antigens used in formulations of vaccines against Neisseria menigitidis were displayed on in vivo assembled polyester beads using a combined bioengineering and conjugation approach. An endotoxin-free mutant of Escherichia coli was engineered to produce translational fusions of antigens (Neisseria adhesin A (NadA) and factor H binding protein (fHbp) derived from serogroup B) to the polyhydroxybutyrate synthase (PhaC), in order to intracellularly assemble polyester beads displaying the respective antigens. Purified beads displaying NadA showed enhanced immunogenicity compared to soluble NadA. Both soluble and particulate NadA elicited functional antibodies with bactericidal activity associated with protective immunity. To expand the antigen repertoire and to design a more broadly protective vaccine, NadA-PhaC beads were additionally conjugated to the capsular polysaccharide from serogroup C. Co-delivery of surface displayed NadA and the capsular polysaccharide induced a strong and specific Th1/Th17 mediated immune response associated with functional bactericidal antibodies. Our findings provide the foundation for the design of multivalent antigen-coated polyester beads as suitable carriers for protein and polysaccharide antigens in order to induce protective immunity.
通过颗粒传递策略可以提高蛋白质和碳水化合物抗原作为疫苗的功效。在这里，使用组合的生物工程和缀合方法，在体内组装的聚酯珠上展示了用于脑膜炎奈瑟氏菌疫苗配方中的蛋白质和碳水化合物抗原。通过工程改造无内毒素的大肠杆菌，以产生抗原（来自 B 群的 Neisseria 粘附素 A（NadA）和因子 H 结合蛋白（fHbp））与聚羟基丁酸酯合酶（PhaC）的翻译融合物，以便在细胞内组装显示各自抗原的聚酯珠。与可溶性 NadA 相比，显示 NadA 的纯化珠显示出增强的免疫原性。可溶性和颗粒状 NadA 均引发了具有与保护性免疫相关的杀菌活性的功能性抗体。为了扩大抗原库并设计更广泛的保护性疫苗，还将 NadA-PhaC 珠与 C 群荚膜多糖缀合。表面展示的 NadA 和荚膜多糖的共同递呈诱导了与功能性杀菌抗体相关的强烈和特异性 Th1/Th17 介导的免疫反应。我们的发现为设计多价抗原涂覆的聚酯珠作为诱导保护性免疫的蛋白质和多糖抗原的合适载体提供了基础。
