Protein Capsular Matrix Vaccines

NERCE项目10：蛋白质胶囊基质疫苗--John J.Mekalanos，Ph.D. 衣壳多糖是参与保护性免疫的主要抗原成分。 被包裹的细菌病原体，如脑膜炎奈瑟菌、肺炎链球菌和 B型流感嗜血杆菌几种生物战剂，如炭疽芽孢杆菌和弗氏杆菌 也表达可能是保护性抗原的荚膜多糖。该项目将探索 针对多种细菌的衣壳多糖的新型疫苗技术的应用。 青少年和成人接种多糖类抗原减轻了疾病负担，但 在为婴幼儿提供保护性免疫方面效果不佳，这些婴幼儿还没有形成 成熟的适应性免疫曲目。在儿童中，包膜多糖等T非依赖性抗原 免疫原性差，不能诱导长期保护性免疫反应。然而，a 多糖类T非依赖性抗原可通过化学方法转化为T依赖性抗原 将多糖连接到蛋白质载体上。这种结合的抗原有效地诱导亲和力。 成熟、同型转换和免疫记忆归因于T依赖的免疫反应。 我们假设疫苗制剂可以刺激同型转换和亲和力成熟。 其中多糖抗原被包裹在也包含载体蛋白的基质中。这些 疫苗制剂，我们称之为蛋白质胶囊基质疫苗(PCMV)，不需要 T非依赖性多糖抗原与蛋白质载体的共价偶联。拟议中的项目 包括对PCMV抗原的持续鉴定。

NERCE Project 10: Protein Capsular Matrix Vaccines - John J. Mekalanos, Ph.D. Capsular polysaccharides are the primary antigenic components involved in protective immunity against encapsulated bacterial pathogens such as Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type b. Several biological warfare agents, such as Bacillus anthracis and Francisella tularensis, also express capsular polysaccharides that are likely protective antigens. This project will explore the utility of a novel vaccine technology directed against capsular polysaccharides from a variety of bacteria. Immunization of adolescents and adults with polysaccharide antigens has reduced disease burden but is ineffective in providing protective immunity to infants and young children, who have not yet developed a mature adaptive immune repertoire. In children, T-independent antigens such as capsular polysaccharides are poorly immunogenic and do not induce long-term protective immune responses. However, a polysaccharide T-independent antigen can be converted into a T-dependent antigen by chemically conjugating the polysaccharide to a protein carrier. This conjugated antigen efficiently induces avidity maturation, isotype switching, and immunological memory attributed to a T-dependent immune response. We hypothesize that isotype switching and affinity maturation can be stimulated by a vaccine preparation in which the polysaccharide antigen is entrapped in a matrix that also contains a carrier protein. These vaccine preparations, which we have called protein capsular matrix vaccines (PCMVs), do not require covalent conjugation of the T-independent polysaccharide antigen to a protein carrier. The proposed project involves continued characterization of PCMV antigens.