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

表达弓形虫致密颗粒蛋白7的流感病毒样颗粒可保护小鼠免受致命性ME49病毒攻击。

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Abstract

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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