Protein Capsular Matrix Vaccines

蛋白胶囊基质疫苗

• 批准号: 7645369
• 负责人: John Joseph Mekalanos
• 金额: $ 27.87万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7645369
• 关键词: Adolescent; Adult; Affinity; Agonist; Animal Model; Anthrax disease; Antigens; Avidity; Bacillus anthracis; Bacteria; Biological Warfare; Carrier Proteins; Charge; Child; Collaborations; Combined Vaccines; Doctor of Philosophy; Drug Formulations; Encapsulated; Flagellin; Francisella tularensis; Glutamic Acid; Haemophilus influenzae type b bacteria; Immune; Immune response; Immunity; Immunization; Immunoglobulin Class Switching; Immunologic Memory; Infant; Infection; Ligands; Molecular; Neisseria meningitidis; O Antigens; Pneumonia; Polysaccharides; Preparation; Prostaglandins A; Proteins; Role; Serotyping; Streptococcus pneumoniae; T-Independent Antigens; Technology; Testing; Tularemia; Vaccine Antigen; Vaccines; burden of illness; capsule; immunogenic; novel vaccines; pathogen

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.

Nerce Project 10：蛋白质胶囊基质疫苗-John J. Mekalanos博士 囊囊多糖是针对保护性免疫的主要抗原成分 封装的细菌病原体，例如脑膜炎奈瑟氏菌，肺炎链球菌和 流感嗜血杆菌b。几种生物战毒剂，例如炭疽芽孢杆菌和弗朗西斯拉 Tularensis，也表达可能是保护性抗原的囊囊多糖。这个项目将探索 一种针对各种细菌的囊膜多糖的新型疫苗技术的实用性。 青少年和成年多糖抗原的免疫负担减轻了疾病负担，但IS 尚未发展为婴儿和幼儿的保护性免疫无效，他们尚未发展 成熟的适应性免疫曲目。在儿童中，独立于T的抗原，例如囊囊多糖 免疫原性不良，不会诱导长期保护性免疫反应。但是， 多糖T独立抗原可以通过化学化转化为T依赖性抗原 将多糖共轭到蛋白质载体上。这种共轭抗原有效地引起了亲和力 成熟，同种型切换和免疫记忆归因于T依赖性免疫反应。 我们假设同型切换和亲和力成熟可以通过疫苗制备刺激 其中多糖抗原被捕获在含载体蛋白的基质中。这些 我们称之为蛋白质囊膜基质疫苗（PCMV）的疫苗制剂不需要 T独立多糖抗原与蛋白质载体的共价结合。拟议的项目 涉及PCMV抗原的持续表征。