Anand Setty Balakrishnan, Gnanasekar Munirathinam, Thangadurai Mani, Prabhu Prince R, Kaliraj Perumal, Ramaswamy Kalyanasundaram
Centre for Biotechnology, Anna University, Chennai 600025, India.
Parasitol Res. 2007 Sep;101(4):981-8. doi: 10.1007/s00436-007-0571-2. Epub 2007 Jun 9.
A homologue of Brugia malayi venom allergen (BmVAH) was cloned from the infective stages (L3) of Wuchereria bancrofti. Sequence analysis showed 90% sequence identity between WbVAH and BmVAH. Recombinant WbVAH was then expressed and purified. VAH from other nematode parasites is being evaluated as potential vaccine candidates. Because W. bancrofti infections are more prevalent than B. malayi, it will significantly benefit using W. bancrofti antigens for vaccine development. In this study, we have evaluated the human immune responses to rWbVAH in putatively immune individuals who live in the endemic regions (endemic normal, EN) to determine the vaccine potential of WbVAH. These responses were then compared to those in infected individuals (microfilaraemic, MF and chronic pathology, CP). Results show that EN subjects carry WbVAH-specific IgG1, IgG2, and IgG3 circulating antibodies. It is interesting to note that CP patients also carried antibodies against WbVAH that was mainly of the IgG3 isotype. Peripheral blood mononuclear cells (PBMC) from EN individuals responded strongly to rWbVAH by proliferating and secreting IFN-gamma. PBMC from MF patients also proliferated in response to rWbVAH but secreted mainly IL-10. Thus, there was a clear dichotomy in the cytokine production by infected patients vs individuals who are putatively immune (EN). Although vaccine potential of WbVAH has not been established yet, our findings suggest that WbVAH mediated immune responses in EN individuals is primarily Th1-biased. Further vaccination studies are underway in animal models to determine the role of WbVAH in protective immunity against W. bancrofti and B. malayi infections.
从班氏吴策线虫的感染期幼虫(L3)中克隆出马来布鲁线虫毒液变应原(BmVAH)的一个同源物。序列分析显示,WbVAH与BmVAH的序列一致性为90%。随后表达并纯化了重组WbVAH。来自其他线虫寄生虫的VAH正在作为潜在的疫苗候选物进行评估。由于班氏吴策线虫感染比马来布鲁线虫更为普遍,使用班氏吴策线虫抗原进行疫苗开发将带来显著益处。在本研究中,我们评估了生活在流行地区的假定免疫个体(地方性正常,EN)对重组WbVAH的人体免疫反应,以确定WbVAH的疫苗潜力。然后将这些反应与感染个体(微丝蚴血症,MF和慢性病理,CP)的反应进行比较。结果显示,EN个体携带WbVAH特异性IgG1、IgG2和IgG3循环抗体。有趣的是,CP患者也携带针对WbVAH的抗体,主要是IgG3同种型。EN个体的外周血单个核细胞(PBMC)对重组WbVAH有强烈反应,表现为增殖并分泌干扰素-γ。MF患者的PBMC对重组WbVAH也有增殖反应,但主要分泌白细胞介素-10。因此,感染患者与假定免疫个体(EN)在细胞因子产生方面存在明显差异。虽然WbVAH的疫苗潜力尚未确定,但我们的研究结果表明,WbVAH介导的EN个体免疫反应主要偏向于Th1型。正在动物模型中进行进一步的疫苗接种研究,以确定WbVAH在针对班氏吴策线虫和马来布鲁线虫感染的保护性免疫中的作用。