呈递刚地弓形虫致密颗粒蛋白7的流感病毒样颗粒保护小鼠免受致命的ME49攻击。

IF 3.9
Nanomedicine (London, England) Pub Date : 2025-09-01 Epub Date: 2025-08-13 DOI:10.1080/17435889.2025.2546769
Jie Mao, Hae-Ji Kang, Su-In Heo, Fu-Shi Quan
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引用次数: 0

摘要

目的:刚地弓形虫致密颗粒抗原7 (GRA7)是一种跨寄生虫生命周期表达的膜相关蛋白,是一种有前景的疫苗靶点。本研究旨在研制一种基于gra7的病毒样颗粒(VLP)疫苗并评价其保护效果。材料与方法:通过杆状病毒表达系统,采用流感M1支架构建GRA7 VLPs。雌性BALB/c小鼠鼻内免疫3次,并口服致死性弓形虫ME49囊。在感染后40天评估体液和细胞免疫反应、脑炎症和寄生虫负担。攻毒后监测体重减轻和存活率。结果:gr7 VLPs免疫后可诱导血清中有较强的弓形虫特异性IgG。在囊肿攻击后,免疫小鼠的肠道、粪便和脑组织中检测到抗体水平升高,并伴有igg分泌细胞、生发中心B细胞、记忆B细胞以及抗原再刺激的脾细胞中CD4+和CD8+ T细胞的活化增强。值得注意的是,接种疫苗的小鼠表现出100%的存活率和持续的体重,同时大脑促炎细胞因子和寄生虫囊肿负担显着减少。结论:GRA7 VLPs具有强大的全身和粘膜免疫能力,对慢性弓形虫病具有显著的保护作用,强调了其作为一种有前景的疫苗平台的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Influenza virus-like particles presenting Toxoplasma gondii dense granule protein 7 protect mice from lethal ME49 challenge.

Aim: Toxoplasma gondii dense granule antigen 7 (GRA7) is a membrane-associated protein expressed across parasite life cycle and represents a promising vaccine target. This study aimed to develop a GRA7-based virus-like particle (VLP) vaccine and assess its protective efficacy.

Materials & methods: GRA7 VLPs were constructed using an influenza M1 scaffold via the baculovirus expression system. Female BALB/c mice were immunized intranasally three times and orally challenged with lethal T. gondii ME49 cysts. Humoral and cellular immune responses, brain inflammation, and parasite burden were evaluated at 40 days post-infection. Body weight reduction and survival rate were monitored after challenge.

Results: GRA7 VLPs induced robust T. gondii-specific IgG in serum after immunization. Following challenge with cysts, elevated antibody levels were detected in intestinal, fecal, and brain tissues, accompanied by enhanced activation of IgG-secreting cells, germinal center B cells, memory B cells, as well as CD4+ and CD8+ T cells in antigen-restimulated splenocytes of vaccinated mice. Notably, vaccinated mice exhibited 100% survival and sustained body weight, alongside a marked reduction in cerebral pro-inflammatory cytokines and parasite cyst burden.

Conclusion: GRA7 VLPs confer strong systemic and mucosal immunity and significant protection against chronic toxoplasmosis, underscoring their potential as a promising vaccine platform.

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