Virus-like Particle Vaccine Containing Toxoplasma gondii Rhoptry Protein 13 Induces Protection against T. gondii ME49 Infection in Mice

Hae-Ji Kang, Ki-Back Chu, Su-Hwa Lee, Min-Ju Kim, Hyunwoo Park, Hui Jin, F. Quan
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引用次数: 6

Abstract

Toxoplasma gondii can infect humans worldwide, causing serious diseases in pregnant women and immunocompromised individuals. T. gondii rhoptry protein 13 (ROP13) is known as one of the key proteins involved in host cell invasion. In this study, we generated virus-like particles (VLPs) vaccine expressing T. gondii rhoptry ROP13 and investigated VLPs vaccine efficacy in mice. Mice immunized with ROP13 VLPs vaccine elicited significantly higher levels of T. gondii-specific IgG, IgG1, IgG2a, and IgA antibody responses following boost immunization and challenge infection, whereas antibody inductions were insignificant upon prime immunization. Differing immunization routes resulted in differing antibody induction, as intranasal immunization (IN) induced greater antibody responses than intramuscular immunization (IM) after boost and challenge infection. IN immunization induced significantly higher levels of IgG and IgA antibody responses from feces, antibody-secreting cells (ASCs), CD4+ T, CD8+ T cells and germinal center B cell responses in the spleen compared to IM immunization. Compared to IM immunization, IN immunization resulted in significantly reduced cyst counts in the brain as well as lesser body weight loss, which contributed to better protection. All of the mice immunized through either route survived, whereas all naïve control mice perished. These results indicate that the ROP13 VLPs vaccine could be a potential vaccine candidate against T. gondii infection.
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含刚地弓形虫虫体蛋白13的病毒样颗粒疫苗诱导小鼠抗刚地弓形虫ME49感染
刚地弓形虫可以在世界范围内感染人类,在孕妇和免疫功能低下的个体中引起严重疾病。弓形虫虫体蛋白13 (ROP13)是参与宿主细胞侵袭的关键蛋白之一。本研究制备了表达弓形虫ROP13的病毒样颗粒(VLPs)疫苗,并在小鼠体内研究了VLPs疫苗的有效性。经ROP13 VLPs疫苗免疫的小鼠,在增强免疫和激发感染后,弓形虫特异性IgG、IgG1、IgG2a和IgA抗体反应水平显著提高,而在初始免疫时,抗体诱导水平不显著。不同的免疫途径导致不同的抗体诱导,如鼻内免疫(in)诱导的抗体应答比肌内免疫(IM)诱导的抗体应答更大。与IM免疫相比,IN免疫诱导的粪便IgG和IgA抗体反应、抗体分泌细胞(ASCs)、CD4+ T、CD8+ T细胞和脾脏生发中心B细胞反应水平显著提高。与IM免疫相比,IN免疫导致脑内囊肿数量显著减少,体重减轻,有助于更好的保护。通过两种途径免疫的所有小鼠都存活了下来,而所有naïve对照组小鼠都死亡了。这些结果表明,ROP13 VLPs疫苗可能是弓形虫感染的潜在候选疫苗。
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