Synthetic glycan conjugates with bacteriophage Qbeta for broad spectrum anti-salmonella vaccines

用于广谱抗沙门氏菌疫苗的合成聚糖与噬菌体 Qbeta 缀合物

基本信息

批准号：
10201474
负责人：
Xuefei Huang
金额：
$ 30万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-16 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10201474
关键词：
Antibodies Antibody Response Antigens Bacteria Bacteriophages Carbohydrates Cell surface Cells Cessation of life Characteristics Complement Development Disease Dose Engineering Enzyme-Linked Immunosorbent Assay Gastroenteritis Generations Glycoconjugates Helper-Inducer T-Lymphocyte Hexoses Hospitalization Immune Sera Immune response Immune system Immunize Immunoglobulin G Infection Lead Length Lipopolysaccharides Methods Multi-Drug Resistance Mus O Antigens Oryctolagus cuniculus Pathogenicity Pattern Polysaccharides Prevention Public Health Reaction Resort Route Salmonella Salmonella Vaccines Salmonella enteritidis Salmonella infections Salmonella paratyphi Salmonella typhi Salmonella typhimurium Southeastern Asia Structure Surface Synthesis Chemistry Time Tumor-Associated Carbohydrate Antigens Typhoid Fever Ursidae Family Vaccines Vertebral column Virus-like particle Work base capsule carbohydrate structure combat design enteritis fighting immunogenic novel pathogenic bacteria prevent response tool vaccine development vaccinology

项目摘要

Salmonella infections (salmonellosis) are a major public health problem throughout the world. With the emergence of multidrug resistant Salmonella strains, there is a pressing need for new methods to prevent salmonellosis. As there are characteristic carbohydrate structures on the surface of Salmonella bacteria, in this project, a collaborative team is formed to develop effective carbohydrate based anti-Salmonella vaccines. Instead of relying on isolated carbohydrates from the pathogenic bacteria, in aim 1, synthetic strategies will be developed to produce structure well defined Salmonella glycans from major pathogenic serovars. In aim 2, Salmonella glycans will be conjugated with a virus like particle, bacteriophage Qβ as potential vaccines targeting specific pathogenic Salmonella strains. This is supported by promising preliminary results that the Qβ glycan conjugates were able to induce high titers (over 80 million ELISA units in rabbits) and long lasting anti-glycan IgG antibodies, which could provide complete protection to mice from lethal challenges by Salmonella bacteria. Building on these results, the Qβ carrier will be engineered to enhance its abilities to further boost anti-Salmonella immune responses. In aim 3, a broad spectrum anti- Salmonella vaccine will be developed, which can provide powerful protection against multiple types of major pathogenic Salmonella by a single vaccine. This can complement well the strain specific vaccines. This work can lead to an exciting new direction for anti-Salmonella vaccine development, providing a much needed new arsenal in fighting salmonellosis.

沙门氏菌感染（沙门氏菌病）是整个过程中的主要公共卫生问题世界。随着多药耐药沙门氏菌菌株的出现，有紧迫的需求用于预防沙门氏菌病的新方法。由于有特征性的碳水化结构在沙门氏菌细菌的表面上，在这个项目中，成立了一个合作团队来发展有效的基于碳水性的抗盐酸疫苗。而不是依靠来自致病细菌的孤立的碳水性，而是在AIM 1中将制定合成策略来产生结构明确的沙门氏菌聚糖主要的致病血清。在AIM 2中，沙门氏菌聚糖将与类似的病毒结合粒子，噬菌体Qβ作为靶向特定致病沙门氏菌的潜在疫苗菌株。这是由Qβ聚糖偶联物是它可以诱导高滴度（超过8000万个ELISA单位）和持久的反聚糖IgG 抗体，可以为小鼠提供完全保护，以免受致命挑战沙门氏菌细菌。在这些结果的基础上，将设计Qβ载体以增强其能力进一步增强抗盐酸免疫反应。在AIM 3中，广谱抗将开发沙门氏菌疫苗，可以为多重提供强大的保护单一疫苗的主要致病沙门氏菌类型。这可以很好地完成压力特定的疫苗。这项工作可能会导致抗盐对疫苗的新方向开发，为抗击沙门氏菌病提供了急需的新阿森纳。