Centre for Biotechnology, Anna University, Guindy, Chennai, 600025, Tamilnadu, India.
Parasitol Res. 2013 Sep;112(9):3203-11. doi: 10.1007/s00436-013-3496-y. Epub 2013 Jul 5.
Filarial parasites infected nearly 160 million of the global population with onchocerciasis and lymphatic filariasis, and further, a billion of people are estimated to be at risk of infection, rendering them among the most prevalent infectious agents in the world today. Given the complexity of their life cycle and the immune evasion mechanisms of these organisms, development of a vaccine remains to be a long-term challenge. Though a number of immunodominant antigens have been characterized, the presence of homologous proteins in humans or the allelic variants are some of the major drawbacks. One of the extensively studied vaccine candidates is abundant larval transcripts (ALT) family of proteins for the following properties: highly regulated expression, abundance, excreted-secreted product of infective stage larvae, and essentially for parasite establishment and survival in the host. In the present study, stage-specific expression of secreted larval acidic protein 1 (SLAP1) was identified; an ALT orthologue from Onchocerca volvulus was cloned, expressed, and purified as a recombinant protein. Immunogenicity of OvSLAP1 was demonstrated with sera and peripheral blood mononuclear cells from endemic regions of Brugia malayi and Wuchereria bancrofti. OvSLAP1 antibodies were predominated by IgG1 and IgG2 in endemic normal (EN) and chronic pathology (CP) subjects. It has also induced marked cellular response as observed by lymphoproliferation assay. The study revealed that OvSLAP1 can segregate humoral (EN mean optical density (OD) = 0.87 ± 0.035, CP mean OD = 0.59 ± 0.029) and cellular (EN mean stimulation index (SI) = 5.87 ± 0.167, CP mean SI = 3.5 ± 0.134) immune responses between EN and CP individuals (P < 0.001), signifying its prophylactic ability and vitality for protection from filarial infections in endemic population.
丝虫寄生虫感染了近 1.6 亿全球人口的盘尾丝虫病和淋巴丝虫病,此外,估计有 10 亿人面临感染风险,使其成为当今世界最普遍的传染病原体之一。鉴于其生命周期的复杂性和这些生物体的免疫逃避机制,疫苗的开发仍然是一个长期挑战。尽管已经确定了许多免疫优势抗原,但在人类中存在同源蛋白或等位基因变异是一些主要的缺点。研究最多的疫苗候选物之一是丰富的幼虫转录本(ALT)家族蛋白,具有以下特性:高度调控表达、丰度、感染期幼虫的排泄-分泌产物,以及对寄生虫在宿主中的建立和存活至关重要。在本研究中,鉴定了分泌性幼虫酸性蛋白 1(SLAP1)的阶段特异性表达;从盘尾丝虫克隆了 ALT 同源物,作为重组蛋白进行了表达和纯化。用来自班氏丝虫和马来丝虫流行地区的血清和外周血单核细胞证明了 OvSLAP1 的免疫原性。OvSLAP1 抗体在流行地区的正常(EN)和慢性病理(CP)个体中主要是 IgG1 和 IgG2。淋巴增殖测定也显示出它诱导了明显的细胞反应。该研究表明,OvSLAP1 可以区分体液(EN 平均光密度(OD)=0.87±0.035,CP 平均 OD=0.59±0.029)和细胞(EN 平均刺激指数(SI)=5.87±0.167,CP 平均 SI=3.5±0.134)免疫反应在 EN 和 CP 个体之间(P<0.001),表明其具有预防能力和活力,可以保护流行地区的人免受丝虫感染。