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首页> 外文期刊>Vaccine >Schistosoma mansoni ex vivo lung-stage larvae excretory-secretory antigens as vaccine candidates against schistosomiasis
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Schistosoma mansoni ex vivo lung-stage larvae excretory-secretory antigens as vaccine candidates against schistosomiasis

机译:曼氏血吸虫离体肺阶段幼虫排泄分泌抗原作为抗血吸虫病的候选疫苗

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Schistosoma mansoni lung-stage larvae are known to be the major target of innate and acquired immunity to schistosomiasis. Lung schistosomula cytosolic or surface membrane antigens are hidden, entirely inaccessible to the host immune system, and hence are not particularly important as vaccine candidates. Conversely, excretory-secretory (E-S) products released from intact, viable, elongated, and contractile schistosomula are ideal potential vaccines, as such molecules can readily play a central role in the induction of local primary and memory immune response effectors that would directly target, surround, and pursue the larvae while negotiating the lung capillaries. Therefore, 6-day-old ex vivo larvae were isolated from mouse or hamster lung cells and used for generation of E-S products, which were shown to elicit strong immune responses and significant (P<0.05) protection against challenge infection in BALB/c mice. Proteomic analysis of E-S molecules following 10x concentration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis identified peptides related to innumerable host and about 15 S. mansoni-specific proteins. Selected S. mansoni-specific E-S peptides prepared in a multiple antigen peptide (MAP) or recombinant form were shownto stimulate considerable specific antibody response and peripheral blood mononuclear cell expression of mRNA for several cytokines in immunized C57BL/6 and BALB/c mice. However, highly significant (P<0.05 to <0.005) reduction in challenge infection worm burden and egg load was recorded only when the immunization conditions in test mice provided the S. mansoni antigen-specific T helper (Th) type response milieu favorable for each immunogen. That was polarized Th1 for S. mansoni aldolase and thioredoxinperoxidase 1 MAPs, polarized Th2 for recombinant 14-3-3-like protein, mixed Th1/Th17 for calpain MAP, and mixed Th1/Th2 for recombinant p18 protein. The findings together indicated that the immune responses issue is as critical as the nature and sourceof the antigen for the development of vaccine against schistosomiasis.
机译:曼氏血吸虫肺部幼虫已知是血吸虫病先天和获得性免疫的主要靶标。肺血吸虫胞质或表面膜抗原是隐藏的,宿主免疫系统完全无法接近,因此作为候选疫苗并不是特别重要。相反,从完整,可行,细长和收缩性血吸虫中释放的排泄分泌(ES)产品是理想的潜在疫苗,因为这类分子可以在诱导直接靶向的局部原发性和记忆性免疫应答效应因子中轻易发挥核心作用,围绕并在与肺毛细血管进行谈判的同时追捕幼虫。因此,从小鼠或仓鼠肺细胞中分离出6天大的离体幼虫,并用于产生ES产品,这些产品在BALB / c小鼠中表现出强烈的免疫应答和显着(P <0.05)的抗感染攻击能力。在10倍浓度和十二烷基硫酸钠-聚丙烯酰胺凝胶电泳后对E-S分子进行蛋白质组学分析,鉴定出与无数宿主和约15种曼氏梭菌特异性蛋白相关的肽。在免疫C57BL / 6和BALB / c小鼠中,以多种抗原肽(MAP)或重组形式制备的选定曼氏梭菌特异性E-S肽可刺激多种细胞因子刺激相当大的特异性抗体反应和外周血单核细胞mRNA表达。但是,只有在试验小鼠的免疫条件提供了对每个人有益的曼氏沙门氏菌抗原特异性T辅助(Th)型应答环境时,才能记录到挑战性感染蠕虫负荷和卵负荷的显着降低(P <0.05至<0.005)。免疫原。对于曼氏葡萄球菌醛缩酶和硫氧还蛋白过氧化物酶1 MAPs,极化Th1,对重组14-3-3-like蛋白极化Th2,对钙蛋白酶MAP极化Th1 / Th17,对重组p18蛋白极化Th1 / Th2。这些发现共同表明,免疫应答问题与开发针对血吸虫病的疫苗的抗原的性质和来源一样重要。

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