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基于 Sm-p80 的 DNA 疫苗为狒狒提供了针对曼氏血吸虫感染的保护水平,可与辐照尾蚴疫苗相当。

Sm-p80-based DNA vaccine provides baboons with levels of protection against Schistosoma mansoni infection comparable to those achieved by the irradiated cercarial vaccine.

机构信息

Department of 1Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

出版信息

J Infect Dis. 2010 Apr 1;201(7):1105-12. doi: 10.1086/651147.

Abstract

To date, no vaccine is available to prevent human schistosomiasis. We have targeted a protein of Schistosoma mansoni that plays an important role in the surface membrane renewal process, a mechanism widely believed to be utilized by the parasite as an immune evasion strategy. Sm-p80 antigen is a promising vaccine target because of its documented immunogenicity, protective efficacy, and antifecundity effects observed in both experimental murine and nonhuman primate models of this infectious disease. In the present study, we report that, in a vector approved for human use (VR1020), an Sm-p80-based DNA vaccine formulation confers a 46% reduction in the worm burden in a baboon (Papio anubis) model. Baboons vaccinated with Sm-p80-VR1020 had a 28% decrease in egg production after challenge with the infectious parasite. Sm-p80-VR1020 vaccine elicited robust immune responses to specific antigen Sm-p80, including immunoglobulin (Ig) G, its subtypes IgG1 and IgG2, and IgA and IgM in vaccinated animals. When stimulated in vitro with recombinant Sm-p80, peripheral blood mononuclear cells and splenocytes from baboons vaccinated with Sm-p80-VR1020 produced considerably higher levels of T helper 1 response-enhancing cytokines (interleukin [IL]-2 and interferon-gamma) than T helper 2 (Th2) response-enhancing cytokines (IL-4 and IL-10). Peripheral blood mononuclear cells produced a significantly higher number of spot-forming units for interferon-gamma than for IL-4 in enzyme-linked immunosorbent spot assays. A mixed T helper 1/T helper 2 type of humoral and T cell responses was generated after immunization with Sm-p80-VR1020. These findings again highlight the potential of Sm-p80 as a promising vaccine candidate for schistosomiasis.

摘要

迄今为止,尚无预防人体血吸虫病的疫苗。我们针对的是曼氏血吸虫的一种蛋白质,该蛋白质在表面膜更新过程中起重要作用,而这种机制被广泛认为是寄生虫利用的一种免疫逃避策略。Sm-p80 抗原是一种很有前途的疫苗靶标,因为它具有免疫原性、保护效力和在这种传染病的实验性鼠和非人类灵长类动物模型中观察到的抗生殖作用。在本研究中,我们报告说,在一种经批准可用于人体的载体(VR1020)中,基于 Sm-p80 的 DNA 疫苗配方可使狒狒(Papio anubis)模型中的蠕虫负担减少 46%。用 Sm-p80-VR1020 接种的狒狒在受到传染性寄生虫的挑战后,其产卵量减少了 28%。Sm-p80-VR1020 疫苗可引发针对特定抗原 Sm-p80 的强烈免疫反应,包括免疫球蛋白(Ig)G、其亚型 IgG1 和 IgG2 以及 IgA 和 IgM。用重组 Sm-p80 体外刺激后,用 Sm-p80-VR1020 接种的狒狒的外周血单核细胞和脾细胞产生的 T 辅助 1 反应增强细胞因子(白细胞介素[IL]-2 和干扰素-γ)的水平明显高于 T 辅助 2(Th2)反应增强细胞因子(IL-4 和 IL-10)。酶联免疫斑点分析显示,外周血单核细胞产生的干扰素-γ斑点形成单位数明显高于 IL-4。用 Sm-p80-VR1020 免疫后产生了一种混合的 T 辅助 1/T 辅助 2 型体液和 T 细胞反应。这些发现再次强调了 Sm-p80 作为血吸虫病有前途的疫苗候选物的潜力。

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