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首页> 外文学位 >Enhancement of the antibody response to a polysaccharide-based vaccine by synthesizing an artificial glycoprotein and using a novel microcapsule delivery system.
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Enhancement of the antibody response to a polysaccharide-based vaccine by synthesizing an artificial glycoprotein and using a novel microcapsule delivery system.

机译：通过合成人工糖蛋白并使用新型微胶囊递送系统，可增强对基于多糖的疫苗的抗体反应。

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摘要

A number of polysaccharide-based vaccines have been developed to stimulate protective immunity against certain encapsulated bacteria. Because of the T cell-independent nature of polysaccharide antigens, the antibody response stimulated by such vaccines is of limited magnitude and restricted isotype, lacks avidity maturation, and is not boosted following reimmunization. Using as a model of the antibody response of mice to the type 3 capsular polysaccharide (S-III) of Streptococcus pneumoniae, the purpose of this project was to develop a vaccine, which by virtue of its formulation and application, would stimulate a heightened antibody response. Three approaches have been taken to develop such a vaccine.;The first approach was to alter the nature of the response stimulated by the antigen to one which is T cell dependent. By conjugating S-III to a protein carrier, the toxoided vaccine of staphylococcal enterotoxin B (SEB), a conjugate vaccine (S-III-SEB) has been synthesized. In contrast to the response stimulated by intraperitoneal immunization with purified S-III, the S-III-specific antibody response stimulated by this S-III-SEB conjugate vaccine was of greater magnitude and altered isotype profile and was boosted by reimmunization.;The second approach was to deliver this conjugate vaccine in a manner to further enhance the antibody response. A novel microcapsule delivery system, where the conjugate vaccine was coated with biocompatible and biodegradable copolymers of DL-lactide and glycolide (DL-lactide-co-glycolide), has been employed. These microcapsules, which are rapidly taken up by phagocytic cells following intraperitoneal or intratracheal injection, effectively delivered antigen to the site of immune response initiation. The plasma anti-S-III response following secondary intraperitoneal immunization with microencapsulated S-III-SEB approached 200 times the level of the response stimulated by an optimal dose of purified S-III.;The third approach was to deliver the vaccine by an immunization route which stimulates antibodies at the site of infection. Intratracheal immunization with microencapsulated S-III-SEB stimulated heightened IgA and IgG anti-S-III concentrations in the circulation and in the secretions which bathe the mucosal surfaces of the lungs and the oral cavity.
机译：已经开发出许多基于多糖的疫苗来刺激针对某些包囊细菌的保护性免疫。由于多糖抗原的不依赖于T细胞的特性，这种疫苗刺激的抗体应答具有有限的大小和同种型，缺乏亲和力成熟，并且在重新免疫后不能增强。作为小鼠对肺炎链球菌3型荚膜多糖（S-III）的抗体反应的模型，该项目的目的是开发一种疫苗，该疫苗的配制和应用将刺激增高的抗体响应。已经开发出了三种方法来开发这种疫苗。第一种方法是将抗原刺激的应答的性质改变为T细胞依赖性的应答。通过将S-III与蛋白载体结合，已合成了葡萄球菌肠毒素B（SEB）的类毒素疫苗，即结合疫苗（S-III-SEB）。与用纯化的S-III腹膜内免疫刺激的反应相反，这种S-III-SEB结合疫苗刺激的S-III特异性抗体反应具有更大的幅度，改变了同种型，并通过重新免疫得到了增强。一种方法是以进一步增强抗体应答的方式递送这种缀合物疫苗。已经使用了新颖的微胶囊递送系统，其中缀合疫苗被DL-丙交酯和乙交酯的生物相容性和可生物降解的共聚物包被（DL-丙交酯-乙交酯）。这些微胶囊在腹膜内或气管内注射后被吞噬细胞迅速吸收，将抗原有效地递送至免疫应答起始位点。微囊化S-III-SEB二次腹膜内免疫后的血浆抗S-III反应达到最佳剂量的纯化S-III刺激反应水平的200倍;第三种方法是通过免疫接种疫苗在感染部位刺激抗体的途径。用微囊化的S-III-SEB进行气管内免疫刺激了循环和淋洗肺和口腔粘膜表面的分泌物中IgA和IgG抗S-III的浓度升高。

著录项

  • 作者

    Meulbroek, Jonathan Allan.;

  • 作者单位

    The University of Alabama at Birmingham.;

  • 授予单位 The University of Alabama at Birmingham.;
  • 学科 Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 1990
  • 页码 166 p.
  • 总页数 166
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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