Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection.
Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection.
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DOI：
10.1371/journal.pntd.0000308
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发表时间：
2008-10-01
影响因子：
3.8
通讯作者：
Oliveira SC
中科院分区：
文献类型：
--
作者：
Cardoso FC;Macedo GC;Gava E;Kitten GT;Mati VL;de Melo AL;Caliari MV;Almeida GT;Venancio TM;Verjovski-Almeida S;Oliveira SC
血吸虫病仍然是一个重大的公共卫生问题。这种疾病影响到全世界2亿人，近8亿人面临感染的风险。虽然针对这种疾病的疫苗开发经历了失败多于成功，但最近使用来自曼氏血吸虫皮层的跨膜蛋白抗原获得了令人鼓舞的结果。我们的小组最近确定了Sm 29，另一种存在于成虫皮层表面的抗原。在这项研究中，我们研究了小鼠细胞免疫反应重组（r）Sm 29和测试这种蛋白作为疫苗候选人。我们首先表明，Sm 29是位于蠕虫和肺阶段童虫通过共聚焦显微镜的表面。其次，用rSm 29免疫小鼠分别使成虫负荷、肠虫卵和肝肉芽肿计数减少51%、60%和50%（p<0.05）。小鼠的保护性免疫与特异性抗Sm 29 IgG 1和IgG 2a的高滴度以及IFN-γ、TNF-α和IL-12的产生升高相关，这是典型的Th 1应答。相对于来自对照小鼠的蠕虫，从rSm 29接种小鼠回收的蠕虫的基因表达分析揭示了495个基因的显著（q<0.01）下调和仅22个基因的上调。在下调的基因中，它们中的许多编码与免疫信号相关的表面抗原和蛋白质，这表明在免疫攻击下，溶酶体减少关键表面蛋白的表达。这项研究表明，Sm 29表面蛋白是一种新的疫苗候选人对血吸虫病，并建议Sm 29疫苗接种与其他保护性的关键表面抗原是下一个合乎逻辑的策略，以提高保护。就发病率和死亡率而言，血吸虫病是最重要的人类蠕虫感染。虽然开发针对这种疾病的疫苗的努力经历了失败，但蛋白质组学研究揭示的新一代表面抗原改变了这种情况。我们的团队已经将先前描述的Sm 29蛋白表征为曼氏血吸虫外皮层中最暴露和表达的抗原之一。对血吸虫病流行区患者的研究显示，抗Sm 29抗体IgG 1和IgG 3水平较高。在这项研究中，共聚焦显微镜分析表明，Sm 29存在于肺阶段的吸虫和蠕虫的表面。重组Sm 29，当用作候选疫苗时，在小鼠中诱导高水平的保护。这种保护与典型的Th 1免疫应答和蠕虫负担、肝肉芽肿和肠内虫卵的减少有关。此外，从接种疫苗的小鼠中回收的蠕虫的微阵列分析显示，编码先前表征的疫苗候选物和/或暴露在表面上的分子的几个基因显著下调，这表明在免疫攻击下的寄生虫体的免疫逃避策略。这些结果表明，Sm 29是一种具有潜在的血吸虫病疫苗的重要抗原。
Schistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present at the adult worm tegument surface. In this study, we investigated murine cellular immune responses to recombinant (r) Sm29 and tested this protein as a vaccine candidate. We first show that Sm29 is located on the surface of adult worms and lung-stage schistosomula through confocal microscopy. Next, immunization of mice with rSm29 engendered 51%, 60% and 50% reduction in adult worm burdens, in intestinal eggs and in liver granuloma counts, respectively (p<0.05). Protective immunity in mice was associated with high titers of specific anti-Sm29 IgG1 and IgG2a and elevated production of IFN-γ, TNF-α and IL-12, a typical Th1 response. Gene expression analysis of worms recovered from rSm29 vaccinated mice relative to worms from control mice revealed a significant (q<0.01) down-regulation of 495 genes and up-regulation of only 22 genes. Among down-regulated genes, many of them encode surface antigens and proteins associated with immune signals, suggesting that under immune attack schistosomes reduce the expression of critical surface proteins. This study demonstrates that Sm29 surface protein is a new vaccine candidate against schistosomiasis and suggests that Sm29 vaccination associated with other protective critical surface antigens is the next logical strategy for improving protection. Schistosomiasis is the most important human helminth infection in terms of morbidity and mortality. Although the efforts to develop a vaccine against this disease have experienced failures, a new generation of surface antigens revealed by proteomic studies changed this scenario. Our group has characterized the protein Sm29 described previously as one of the most exposed and expressed antigens in the outer tegument of Schistosoma mansoni. Studies in patients living in endemic areas for schistosomiasis revealed high levels of IgG1 and IgG3 anti-Sm29 in resistant individuals. In this study, confocal microscope analysis showed Sm29 present in the surface of lung-stage schistosoluma and adult worms. Recombinant Sm29, when used as vaccine candidate, induced high levels of protection in mice. This protection was associated with a typical Th1 immune response and reduction of worm burden, liver granulomas and in intestinal eggs. Further, microarray analysis of worms recovered from vaccinated mice showed significant down-regulation of several genes encoding previously characterized vaccine candidates and/or molecules exposed on the surface, suggesting an immune evasion strategy of schistosomes under immune attack. These results demonstrated that Sm29 as one of the important antigens with potential to compose a vaccine against schistosomiasis.
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影响因子：
2.8
作者：
Bergquist, NR
通讯作者：
Bergquist, NR
影响因子：
2.1
作者：
Gobert, Geoffrey N.;McInnes, Russell;McManus, Donald P.
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McManus, Donald P.
影响因子：
3.8
作者：
Dillon GP;Feltwell T;Skelton J;Coulson PS;Wilson RA;Ivens AC
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Ivens AC
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1.5
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Dinguirard, N;Yoshino, TP
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Yoshino, TP
影响因子：
168.9
作者：
King, CH;Dickman, K;Tisch, DJ
通讯作者：
Tisch, DJ