PREPARATION OF BACTERIAL POLYSACCHARIDE IMMUNE GLOBULIN

细菌多糖免疫球蛋白的制备

• 批准号: 3127711
• 负责人: George R Siber
• 金额: $ 21.22万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-08-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3127711
• 关键词: Alaskan Native American; Haemophilus influenzae; Haemophilus influenzae vaccines; Hispanic Americans; Native Americans; Neisseria meningitidis; Neisseria meningitidis vaccine; Streptococcus pneumoniae; Streptococcus vaccine; affinity chromatography; antibacterial antibody; antibody specificity; bacterial disease; bacterial polysaccharides; child (0-11); communicable disease control; diagnosis design /evaluation; diagnostic tests; enzyme linked immunosorbent assay; human subject; human therapy evaluation; human tissue; immunoconjugates; immunoglobulin G; immunoglobulins; immunological substance; laboratory rat; passive immunization; pediatric pharmacology; rheumatoid factor

Bacterial Polysaccharide Immune Globulin (BPIG) is prepared from donors immunized with H. influenzae b(Hib) pneumococcal and meningococcal vaccines. With previous NIAID support, BPIG has been prepared, characterized, and shown to be efficacious in preventing bacteremic Hib infections in high risk Apache infants. With separate funding from NIAID, a clinical trial to evaluate efficacy against systemic pneumococcal infections is underway and a demonstration project to introduce BPIG into general use to prevent HIB infections in Eskimo infants of the Yukon-Kuskokwim Delta is scheduled to begin in May 1989. The proposed studies are designed to improve further the methods for preparing BPIG, to characterize more precisely the anticapsular antibodies (Abs) in immunized adults and in BPIG, and to develop better standardized assays for Hib, pneumococcal, and meningococcal polysaccharide (Ps) Abs. In order to maximize the Ab response of plasma donors to Ps antigens, we will immunize them with more immunogenic Ps-protein conjugate vaccines and evaluate the quantity and quality of the IgG Ab produced. Alternative and potentially inexpensive methods to enrich Ps Abs will be explored by determining whether affinity chromatography with oligosaccharides can be used to purify Hib Ab from the globulin of unimmunized donors. The pharmacology of BPIG containing higher concentrations of Ab to Hib and to carrier proteins will be examined in high risk groups. Combination passive-active immunization regimens utilizing BPIG and Hib and pneumococcal conjugate vaccines will be examined. Standardized ELISA assays for Ab to Hib, pneumococci and meningococci will be developed and calibrated. The activities of Hib Ps Abs differing in IgG subclass, light chain composition, and G2m(n) allotype will be examined in binding assays, functional assays and in experimental infection. The role of Ab affinity and rheumatoid factors in altering Hib Ps Ab activities in these assays will also be examined. These closely interrelated studies will enhance our basic understanding of the human Ab response to Ps and the functional mechanisms underlying Ab binding to Ps. In addition, they will result in the development of improved methods for immunoprophylaxis of encapsulated bacterial infections in high risk groups. Groups that might benefit from passive immunization include American Indian and Alaskan Eskimo infants, children on cancer chemotherapy with asplenia, sickle cell disease or B cell immunodeficiencies, and secondary contacts of Hib or meningococcal infections.

通过用细菌多糖免疫球蛋白（BPIG）制备 供体肺炎（HIB）肺炎球菌和 脑膜炎球菌疫苗。 在以前的NIAID支持下，Bpig拥有 被准备，表征和证明是有效的 防止高风险apache婴儿中的细菌性HIB感染。 通过临床试验Niaid的单独资金来评估 对全身性肺炎球菌感染的功效正在进行中，并且正在进行 一个演示项目，将BPIG引入一般用途 防止育空地区爱斯基摩婴儿的HIB感染 Delta计划于1989年5月开始。 拟议的研究旨在进一步改善方法 为了准备BPIG，以更精确地表征 免疫成年人和BPIG中的抗囊抗体（ABS）， 并为HIB，肺炎球菌开发更好的标准化测定 和脑膜炎球菌多糖（PS）ABS。 为了最大化 血浆供体对PS抗原的AB反应，我们将免疫 它们采用更多免疫原性的PS蛋白结合疫苗和 评估产生的IgG AB的数量和质量。 富含PS ABS的替代和潜在廉价的方法 将通过确定亲和力色谱法探索 寡糖可用于从 无免疫供体的球蛋白。 BPIG的药理学含有较高浓度的AB 将对HIB和载体蛋白进行高风险检查 组。 组合被动活性免疫方案 利用BPIG，HIB和肺炎球菌结合疫苗将 被检查。 标准化的ELISA分析用于AB到HIB，肺炎球菌和 将开发和校准脑膜炎球菌。 活动 HIB PS ABS的IgG亚类，轻链组成不同， 和G2M（n）同种型将在结合测定中检查， 功能测定和实验感染。 AB的角色 改变Hib PS AB活动的亲和力和类风湿因素 在这些测定中也将进行检查。 这些紧密相互关联的研究将增强我们的基本 了解人类AB对PS和功能的反应 AB与PS结合的机制。 此外，他们将 导致开发改进的方法 封装的细菌感染的免疫预防 风险群体。 可能受益于被动免疫的团体包括 美洲印第安人和阿拉斯加爱斯基摩人，癌症儿童 化学疗法，镰状细胞疾病或B细胞 HIB或HIB的次要接触或 脑膜炎球菌感染。