用脂质抗原设计的细菌幽灵作为流产衣原体无佐剂疫苗。

IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY
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引用次数: 0

摘要

细菌幽灵(BGs)因其固有的佐剂特性和高效的抗原递送能力而成为新型疫苗递送平台。然而,要针对不同的抗原对其进行改造,需要有效的工程策略。本研究利用广泛使用的细菌表面展示载体 lpp'-ompA 嵌合体对大肠杆菌鬼臼毒素(E. coli)进行了改造,将其与流产衣原体(C. abortus)的保护性抗原巨噬细胞感染性增效剂(MIP)进行了融合,并在小鼠模型中对其保护效果进行了评估。MIP 融合蛋白的累积量占鬼魂总蛋白质量的 1.2%,而且在转运到 BG 表面时,相当一部分蛋白被修饰成脂蛋白。脂化的MIP修饰重组大肠杆菌鬼蛋白(rECG-lpp'-MIP)能有效促进抗原递呈细胞(APCs)摄取抗原,并在体内和体外刺激APCs活化。使用rECG-lpp'-MIP和无佐剂免疫可诱导强烈的特异性体液反应和Th1型细胞免疫反应,从而显著提高小鼠流产葡萄球菌感染的清除率并减少子宫的病理损伤。总之,本研究证明了用脂质化抗原修饰的重组大肠杆菌鬼臼毒素有助于开发有效的流产葡萄球菌疫苗,并有助于开发通用的无佐剂疫苗平台。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bacterial ghosts engineered with lipidated antigens as an adjuvant-free vaccine for Chlamydia abortus
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.
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来源期刊
CiteScore
10.70
自引率
8.60%
发文量
951
审稿时长
72 days
期刊介绍: The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.
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