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Vaccination with recombinant adenovirus expressing multi-stage antigens of Toxoplasma gondii by the mucosal route induces higher systemic cellular and local mucosal immune responses than with other vaccination routes

机译:与其他疫苗接种途径相比,通过粘膜途径接种表达弓形虫多阶段抗原的重组腺病毒可诱导更高的全身细胞和局部粘膜免疫应答

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Toxoplasmosis caused by Toxoplasma gondii, an obligate intracellular protozoan, is a cause of congenital disease and abortion in humans and animals. Various vaccination strategies against toxoplasmosis in rodent models have been used in the past few decades; however, effective vaccines remain a challenge. A recombinant adenovirus vaccine expressing ubiquitin-conjugated multi-stage antigen segments (Ad-UMAS) derived from different life-cycle stages of T. gondii was constructed previously. Here, we compared the immune responses and protection effects in vaccination of mice with Ad-UMAS by five vaccination routes including intramuscular (i.m.), intravenous (i.v.), subcutaneous (s.c.), intraoral (i.o.), and intranasal (i.n.). Much higher levels of T. gondii-specific IgG and IgA antibodies were detected in the sera of the intraoral and intranasal vaccination groups on day 49 compared with controls (p?
机译:弓形虫是专性细胞内原生动物引起的弓形虫病,是人类和动物先天性疾病和流产的原因。在过去的几十年中,已经在啮齿动物模型中使用了多种针对弓形虫的疫苗接种策略。然而,有效的疫苗仍然是一个挑战。先前构建了一种重组腺病毒疫苗,该疫苗表达了来自弓形虫不同生命周期阶段的泛素结合的多阶段抗原区段(Ad-UMAS)。在这里,我们通过5种疫苗接种途径(包括肌内(i.m.),静脉内(i.v.),皮下(s.c.),口内(i.o.)和鼻内(i.n.))比较了用Ad-UMAS接种小鼠的免疫反应和保护作用。与对照组相比,在第49天,在口腔内和鼻内疫苗接种组的血清中检测到了更高的弓形虫特异性IgG和IgA抗体水平(p≤0.05)。经鼻和经口免疫的小鼠中CD8 + T细胞的百分比大于经肌内免疫的小鼠(p≤0.05)。在经鼻免疫的组中检测到最高水平的IL-2和IFN-γ,并且经口服和经鼻途径免疫的小鼠的脾细胞增殖活性显着增强。此外,在口腔内和鼻内组中观察到较高的存活率(50%)和较低的囊肿数量均表明,Ad-UMAS在保护小鼠免受粘膜弓形虫感染方面更为有效。 Ad-UMAS可能是一种有效且安全的粘膜候选疫苗,可以保护动物和人类免受弓形虫的感染。

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