Protein Capsular Matrix Vaccines

点击翻译按钮获取中文摘要

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.