Developing a novel strategy to uncover vaccine targets in bacterial pathogens

开发一种新策略来发现细菌病原体中的疫苗靶点

• 批准号: 8891081
• 负责人: Andrew Camilli
• 金额: $ 24.75万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8891081
• 关键词: Antibodies; Antigens; Bacteria; Carbohydrates; Cells; Characteristics; Disease; Escherichia coli; Genes; Genetic; Goals; Immune; Immune response; Immunity; Immunization; Immunologic Surveillance; In Vitro; Incidence; Individual; Infection; Left; Lung; Maps; Measures; Mediating; Membrane Proteins; Methods; Modeling; Mono-S; Mus; Mutation; Nasopharynx; Pneumococcal vaccine; Polysaccharides; Proteins; Proteolysis; Reporting; Role; Serotyping; Serum; Streptococcus pneumoniae; Testing; Vaccine Antigen; Vaccines; Virulence; base; cost; fitness; genome editing; genome-wide; genome-wide analysis; high throughput screening; immunogenic; in vivo; mutant; novel strategies; pathogen; protein expression; public health relevance; vaccine development; vaccine evaluation

 DESCRIPTION (provided by applicant): Current capsular polysaccharide-based Streptococcus pneumoniae vaccines are too expensive for their use in most of the world and result in protection to only a subset of circulating strains, which varies geographically. In addition, the incidence of disease caused by serotypes not covered in the vaccines is increasing as these strains fill the niche of the eliminated serotypes, a phenomenon referred to as serotype replacement. Thus, there is a need for the development of vaccines with broader, serotype-independent coverage. Protein-based vaccines that target conserved surface proteins have the potential to provide broad coverage at lower cost. Despite reports of the existence of over two hundred S. pneumoniae surface proteins, those that possess desirable characteristics for inclusion in a vaccine, namely eliciting a protective immune response, a high level of conservation among S. pneumoniae strains, and being essential for viability and/or virulence in order to limit immune escape, are much more limited in number. We hypothesize that functional redundancy is a major reason for the dispensability of many individual surface proteins. We recently used a genome-wide screen based on transposon-sequencing (Tn-seq) to identify a small set of essential surface proteins. In this project we will use Tn-seq for genetic interaction mapping to identify S. pneumoniae surface proteins that are functionally redundant. We will test a subset of singly essential and functionally redundant proteins as mono- and multivalent vaccines, respectively. This project will reveal a new set of protective S. pneumoniae antigens and will generate a new strategy of vaccine development against pathogens.

 描述（通过应用程序证明）：当前基于胶囊的链球菌肺炎疫苗太昂贵了，对于它们的大部分地区使用而言，它们都可以保护疫苗，从而使疫苗中未覆盖的血清型含量。因此，消除血清型的细分是，需要开发具有较宽的血清型蛋白质疫苗，以较宽那些具有理想的特征，可以纳入疫苗反应，肺炎链球菌菌株之间的高水平保守性，以及对于limmune逃生的限制，我们假设功能性冗余是使其具有可分配性的主要原因。许多个人表面蛋白。 映射肺炎链球菌蛋白分别为单一疫苗。