IMMUNOLOGIC STUDIES ON SCHISTOSOMIASIS

血吸虫病的免疫学研究

• 批准号: 3822010
• 负责人: A SHER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3822010
• 关键词: Bacillus Calmette Guerin vaccine; anthelmintics; disease /disorder model; helminthic antigen; human therapy evaluation; human tissue; humoral immunity; immunological substance; immunopathology diagnosis; immunosuppression; isoquinolines; major histocompatibility complex; microorganism immunology; monoclonal antibody; parasitic disease chemotherapy; schistosomiasis

The aim of this project is to study mechanisms of immunity and immune evasion in schistosomiasis with the ultimate goal of developing an experimental vaccine employing defined antigens. A. Vaccination trials with purified paramyosin. Affinity purified or biochemically isolated paramyosin was shown to confer significant protection against challenge infection in 10 out of 12 experiments employing intradermal vaccination with BCG while vaccination with schistosome myosin or heterologous paramyosin was ineffective. However, schistosome extracts depleted of paramyosin were also protective suggesting the existence of other important immunogens in the intradermal model. B. Identification of E/S antigens recognized by vaccine antibodies. Metabolically labeled lung-stage schistosomula were shown to release four antigens of 30, 36, 64, and 100 Kd which are specifically recognized by mice multiply vaccinated with irradiated cercariae. A monoclonal antibody was produced against the 100 Kd component. These antigens are being investigated as new candidate vaccine immunogens. C. Dependence on antibody of praziquantel therapy. By assaying the binding of monoclonal antibodies to praziquantel treated worms recovered from athymic mice, an antigen of 200 Kd was identified which is specifically exposed as a result of drug treatment and therefore is a candidate target for the antibody response previously shown to be required in praziquantel therapy.

该项目的目的是研究免疫机制， 血吸虫病的免疫逃避， 开发使用确定抗原的实验疫苗。 A. 用纯化的副肌球蛋白进行疫苗接种试验。 亲和纯化 或生化分离的副肌球蛋白被证明赋予 在12例中的10例中对攻毒感染有显著保护作用 使用BCG皮内接种的实验， 用亲体肌球蛋白或异源副肌球蛋白接种 是无效的。 然而，令人讨厌的提取物耗尽了 副肌球蛋白也有保护作用，表明存在其他的 在皮内模型中的重要免疫原。 B。 疫苗识别E/S抗原的鉴定 抗体的 代谢标记的肺期童虫为 显示释放30、36、64和100 Kd的四种抗原， 被多次接种的小鼠特异性识别 辐射尾蚴 产生了一种单克隆抗体 相对于100 Kd组分。 这些抗原被 作为新的候选疫苗免疫原进行研究。 C. 吡喹酮治疗的抗体依赖性。 通过测定 单克隆抗体与吡喹酮的结合 从无胸腺小鼠回收的蠕虫， 已确定的药物暴露 因此是抗体的候选靶点 先前显示吡喹酮治疗中需要的反应。