Department of Public Health Laboratory Sciences, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610061, China.
Department of Public Health Laboratory Sciences, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610061, China.
Int J Pharm. 2023 Sep 25;644:123275. doi: 10.1016/j.ijpharm.2023.123275. Epub 2023 Jul 27.
Membrane vesicles (MVs) derived from Listeria monocytogenes (LM) have a natural nanoscale size and contain a variety of bacterial components. We speculated that LM MVs may be a novel delivery vector, but it is necessary to evaluate the safety and immunogenicity of LM MVs in vivo. Here, we isolated LM MVs and tested their safety and immunogenicity both in vitro and in vivo. The results showed that LM MVs stimulated RAW264.7 cells and DC2.4 cells to secrete the inflammatory cytokines IL-1β, TNF-α, IL-6 and IL-10. Intraperitoneal injection of LM MVs at 80 μg per C57BL/6 mouse did not cause lethal effects or irreversible pathological changes in major organs, indicating that LM MVs were safe. Intraperitoneal immunization of C57BL/6 mice twice with LM MVs mainly induced a high level of LM MV-specific IgG antibodies. In addition, we subcutaneously injected C57BL/6 mice with a mixture of ovalbumin and LM MVs and found that LM MVs exhibited a humoral immune adjuvant effect equal to that of the same amount of alum. The results of this study indicated that LM MVs have good safety and effective immunogenicity and may act as humoral immune adjuvants. Therefore, LM MVs are a potential new choice for antigen and drug delivery vectors.
李斯特菌(Listeria monocytogenes,LM)来源的膜泡(MVs)具有天然的纳米级尺寸,并包含多种细菌成分。我们推测 LM MVs 可能是一种新型的递送载体,但有必要在体内评估 LM MVs 的安全性和免疫原性。在这里,我们分离了 LM MVs,并在体外和体内测试了它们的安全性和免疫原性。结果表明,LM MVs 刺激 RAW264.7 细胞和 DC2.4 细胞分泌炎症细胞因子 IL-1β、TNF-α、IL-6 和 IL-10。腹腔内注射 80μg/只 C57BL/6 小鼠的 LM MVs 不会引起致命作用或主要器官不可逆的病理变化,表明 LM MVs 是安全的。两次腹腔内免疫接种 C57BL/6 小鼠的 LM MVs 主要诱导高水平的 LM MV 特异性 IgG 抗体。此外,我们将卵清蛋白和 LM MVs 的混合物皮下注射到 C57BL/6 小鼠中,发现 LM MVs 具有与相同量的明矾相当的体液免疫佐剂效应。这项研究的结果表明,LM MVs 具有良好的安全性和有效的免疫原性,可能作为体液免疫佐剂。因此,LM MVs 是抗原和药物递送载体的一种有潜力的新选择。