Mucosal Immune Responses in Hookworm Infection

钩虫感染的粘膜免疫反应

• 批准号: 6854871
• 负责人: RICHARD D BUNGIRO
• 金额: $ 8.18万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6854871
• 关键词: Nematoda; active immunization; anemia; antibody; cholera toxin; cytokine; enzyme linked immunosorbent assay; hamsters; host organism interaction; immune response; mucosal immunity; parasite infection mechanism; parasitism; polymerase chain reaction; recombinant proteins; western blottings

DESCRIPTION (provided by the applicant): Hookworms remain a major health burden in the developing world, with over one billion persons infected and hundreds of millions suffering from clinically relevant pathology. Substantial future reduction of hookworm disease will likely require the joining of conventional control strategies with novel approaches such as vaccines aimed at ameliorating the clinical sequelae caused by blood feeding adult parasites. Vaccine development will be most efficient if protective immune responses are identified and characterized in suitable animal models. Adult blood feeding hookworms residing in the host intestine secrete various proteins that are known to induce robust systemic immune responses. By contrast, mucosal immune responses in and around the site of attachment are not as well described. We hypothesize that adult hookworms residing in the host intestine induce specific mucosal immune responses in both the humoral and cellular compartments, and that these in turn play a role in acquired resistance to hookworm disease. We further hypothesize that mucosal vaccination may be employed to artificially induce resistance to hookworm infection and/or disease. Accordingly, the aim of this project will be to characterize mucosal immune responses in the hamster model of Ancylostoma ceylanicum hookworm infection to the antibody, cellular, and cytokine levels. A mucosal immunization protocol will be optimized using soluble hookworm extracts delivered by the oral route. Immunogenicity of mucosal immunization will be evaluated using enzyme-linked immunosorbent assay and immunoblot, and protective efficacy will be assessed using clinical measurements of anemia, growth, and worm burden. The optimized mucosal immunization protocol will then be used to evaluate the protective efficacy of adult hookworm antigens which have been previously identified and expressed as recombinant) proteins. These studies are expected to further our understanding of host-parasite immunological interaction and advance hookworm vaccine research through the development of novel immunization techniques.

描述（由申请人提供）：钩虫仍然是发展中世界的一个主要健康负担，有超过10亿人受到感染，数亿人患有临床相关病理。今后大幅度减少钩虫病可能需要将传统控制策略与新方法结合起来，例如旨在改善吸血成年寄生虫引起的临床后遗症的疫苗。如果在适当的动物模型中确定和描述保护性免疫反应，疫苗开发将是最有效的。寄生在宿主肠道内的成年吸血钩虫分泌各种蛋白质，已知这些蛋白质可诱导强大的全身免疫反应。相比之下，附着部位内和周围的粘膜免疫反应没有得到很好的描述。我们假设，寄生在宿主肠道中的成年钩虫在体液和细胞区室中诱导特异性粘膜免疫反应，而这些反应反过来又在钩虫病的获得性抗性中发挥作用。我们进一步假设，粘膜接种可能用于人工诱导对钩虫感染和/或疾病的抗性。因此，本项目的目的将是表征兔钩虫感染仓鼠模型的粘膜免疫反应对抗体、细胞和细胞因子水平的影响。粘膜免疫方案将通过口服途径使用可溶性钩虫提取物进行优化。粘膜免疫的免疫原性将通过酶联免疫吸附试验和免疫印迹进行评估，保护效果将通过贫血、生长和蠕虫负荷的临床测量来评估。优化后的粘膜免疫方案将用于评估成人钩虫抗原的保护效果，这些抗原先前已被鉴定并以重组蛋白的形式表达。这些研究有望进一步加深我们对宿主-寄生虫免疫相互作用的理解，并通过开发新的免疫技术推进钩虫疫苗的研究。