Influenza virus-like particles presenting <i>Toxoplasma gondii</i> dense granule protein 7 protect mice from lethal ME49 challenge

<i>Toxoplasma gondii</i> 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. 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 <i>T. gondii</i> 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. GRA7 VLPs induced robust <i>T. gondii</i>-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. GRA7 VLPs confer strong systemic and mucosal immunity and significant protection against chronic toxoplasmosis, underscoring their potential as a promising vaccine platform.

刚地弓形虫（Toxoplasma gondii）致密颗粒抗原7（GRA7）是一种贯穿寄生虫整个生活周期表达的膜相关蛋白，是极具潜力的疫苗靶标。本研究旨在开发基于GRA7的病毒样颗粒（VLP）疫苗，并评估其保护效力。本研究通过杆状病毒表达系统（baculovirus expression system），以流感M1支架构建了GRA7 VLP。将雌性BALB/c小鼠经鼻内免疫三次，随后经口攻毒致死性刚地弓形虫ME49包囊。于感染后40天，评估小鼠的体液与细胞免疫应答、脑部炎症及寄生虫载量，并于攻毒后监测其体重变化与存活率。免疫后，GRA7 VLP可诱导小鼠血清中产生强效的刚地弓形虫特异性IgG。经包囊攻毒后，免疫小鼠的肠道、粪便及脑组织中抗体水平显著升高；同时，在抗原再刺激的免疫小鼠脾细胞中，IgG分泌细胞、生发中心B细胞、记忆B细胞以及CD4阳性和CD8阳性T细胞的激活水平均得到增强。值得注意的是，免疫小鼠全部存活且体重维持稳定，同时脑部促炎细胞因子水平与寄生虫包囊载量均显著降低。GRA7 VLP可诱导强烈的系统性与黏膜免疫，对慢性弓形虫病提供显著保护，凸显了其作为极具潜力的疫苗平台的应用价值。

搜集汇总

背景与挑战

背景概述

该数据集总结了基于弓形虫致密颗粒蛋白7（GRA7）的流感病毒样颗粒疫苗的研究，通过鼻内免疫小鼠，成功诱导了强烈的体液和细胞免疫反应，实现了100%的生存率并显著降低了脑部寄生虫负担。研究结果表明，该疫苗具有强大的系统和黏膜免疫保护作用，是预防慢性弓形虫病的有前景的疫苗平台。