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Protective Efficacy Induced by Virus-like Particles Expressing Dense Granule Protein 5 of .

作者信息

Heo Su In, Kang Hae-Ji, Mao Jie, Yang Zhao-Shou, Ahmed Md Atique, Quan Fu-Shi

机构信息

Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.

Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute (CRI), Kyung Hee University, Seoul 02447, Republic of Korea.

出版信息

Vaccines (Basel). 2025 Jul 24;13(8):787. doi: 10.3390/vaccines13080787.

Abstract

() causes severe disease in immunocompromised individuals and pregnant women, underscoring the urgent need for effective vaccines against toxoplasmosis. The dense granule protein 5 (GRA5) of plays a key role in parasitic cyst formation. This study evaluated the protective immune responses induced by a virus-like particle (VLP) vaccine expressing the -derived antigen GRA5 in a mouse model challenged with the ME49 strain of . GRA5 VLPs were generated using a baculovirus expression system, and VLP formation was confirmed by Western blotting and visualized using transmission electron microscopy. Mice were intranasally immunized with GRA5 VLPs three times at 4-week intervals to induce immune responses, followed by infection with ME49. Intranasal immunization with GRA5 VLPs induced parasite-specific IgG antibody responses in the serum and both IgG and IgA antibody responses in the brain. Compared to the non-immunized group, immunized mice exhibited significantly higher levels of germinal center B cells and antibody-secreting cell responses. Moreover, the VLP vaccine suppressed the production of IFN-γ and IL-6 cytokines, leading to a significant reduction in brain inflammation and decreased cyst counts following lethal challenge with ME49 infection. These findings suggest that the GRA5 VLP vaccine derived from elicits a protective immune response, highlighting its potential as an effective vaccine candidate against toxoplasmosis.

摘要

()在免疫功能低下的个体和孕妇中会引发严重疾病,这凸显了迫切需要有效的抗弓形虫疫苗。弓形虫的致密颗粒蛋白5(GRA5)在寄生虫囊肿形成中起关键作用。本研究在受到弓形虫ME49株攻击的小鼠模型中,评估了表达弓形虫来源抗原GRA5的病毒样颗粒(VLP)疫苗诱导的保护性免疫反应。使用杆状病毒表达系统产生GRA5 VLP,并通过蛋白质免疫印迹法确认VLP的形成,并用透射电子显微镜观察其形态。小鼠每隔4周鼻内免疫三次GRA5 VLP以诱导免疫反应,随后感染弓形虫ME49株。鼻内免疫GRA5 VLP可在血清中诱导寄生虫特异性IgG抗体反应,并在脑中诱导IgG和IgA抗体反应。与未免疫组相比,免疫小鼠的生发中心B细胞水平和抗体分泌细胞反应显著更高。此外,VLP疫苗抑制了IFN-γ和IL-6细胞因子的产生,导致在受到弓形虫ME49感染致死攻击后脑部炎症显著减轻,囊肿数量减少。这些发现表明,源自弓形虫的GRA5 VLP疫苗可引发保护性免疫反应,突出了其作为抗弓形虫有效候选疫苗的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c09c/12390477/d005adaa133b/vaccines-13-00787-g001.jpg

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