Protein Capsular Matrix Vaccines

NERCE项目10：蛋白胶囊基质疫苗- John J. Mekalanos，Ph.D. 荚膜多糖是参与抗病毒的保护性免疫的主要抗原成分。 包封的细菌病原体，如脑膜炎奈瑟氏菌、肺炎链球菌，和 流感嗜血杆菌B型。几种生物战剂，如炭疽杆菌和弗朗西斯菌 土拉热菌也表达可能是保护性抗原荚膜多糖。该项目将探索 针对来自多种细菌的荚膜多糖的新型疫苗技术的实用性。 用多糖抗原对青少年和成人进行免疫接种可降低疾病负担， 在为婴儿和幼儿提供保护性免疫方面效果不佳， 成熟的适应性免疫库。在儿童中，T非依赖性抗原如荚膜多糖 免疫原性差，不能诱导长期保护性免疫应答。但 多糖T非依赖性抗原可以通过化学方法转化为T依赖性抗原， 将所述多糖缀合至蛋白质载体。这种结合的抗原有效地诱导亲合力 成熟、同种型转换和归因于T依赖性免疫应答的免疫记忆。 我们假设同种型转换和亲和力成熟可以通过疫苗制剂刺激 其中多糖抗原包埋在还含有载体蛋白的基质中。这些 疫苗制剂，我们称为蛋白质包膜基质疫苗（PCMV），不需要 T-非依赖性多糖抗原与蛋白质载体的共价缀合。拟建项目 涉及PCMV抗原的持续表征。

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.