State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730000, China; College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730000, China.
Int J Pharm. 2024 Dec 5;666:124801. doi: 10.1016/j.ijpharm.2024.124801. Epub 2024 Oct 4.
Bacterial ghosts (BGs) provide novel vaccine delivery platforms because of their inherent adjuvant properties and efficient antigen delivery capabilities. However, effective engineering strategies are required to modify them for different antigens. In this study, the Escherichia coli (E. coli) ghost was modified by using a lpp'-ompA chimera, a widely used bacterial surface display vector, with a protective antigen macrophage infectivity potentiator (MIP) of Chlamydia abortus (C. abortus), and its protective effect was evaluated in a mouse model. The MIP fusion protein accumulated at 1.2% of the ghost total protein mass and a significant portion of the protein was modified into lipoproteins upon translocation to the BG surface. Lipidated MIP-modified recombinant E. coli ghosts (rECG-lpp'-MIP) effectively promoted antigen-presenting cells (APCs) uptake of antigens and stimulated APCs activation in vivo and in vitro. Immunization with rECG-lpp'-MIP and no adjuvant induced intense specific humoral responses as well as Th1-biased cellular immune responses, which significantly improved the efficiency of C. abortus infection clearance in mice and reduced pathological damage to the uterus. In summary, this study demonstrates that recombinant E. coli ghosts modified with lipidated antigens could help to develop an effective C. abortus vaccine and aid in the development of a universal adjuvant-free vaccine platform.
细菌体（BGs）因其固有的佐剂特性和高效的抗原传递能力，为新型疫苗的提供了载体。然而，为了使它们适用于不同的抗原，需要有效的工程策略来对其进行修饰。在这项研究中，使用广泛应用于细菌表面展示载体的 lpp'-ompA 嵌合体修饰了大肠杆菌（E. coli）体，其中包含了衣原体流产（C. abortus）的保护性抗原巨噬细胞感染增强剂（MIP），并在小鼠模型中评估了其保护效果。MIP 融合蛋白在细菌体总蛋白质量的 1.2%处积累，并且大量蛋白质在转运到 BG 表面时被修饰成脂蛋白。脂化的 MIP 修饰的重组大肠杆菌体（rECG-lpp'-MIP）有效地促进了抗原呈递细胞（APC）摄取抗原，并在体内和体外刺激了 APC 的激活。用 rECG-lpp'-MIP 免疫接种，无需佐剂，就可诱导强烈的特异性体液反应和 Th1 偏向的细胞免疫反应，这显著提高了清除小鼠体内 C. abortus 感染的效率，并减轻了对子宫的病理损伤。总之，这项研究表明，用脂化抗原修饰的重组大肠杆菌体可有助于开发有效的 C. abortus 疫苗，并有助于开发通用的无佐剂疫苗平台。
