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）是整个世界的一个主要公共卫生问题随着多重耐药沙门氏菌菌株的出现，迫切需要。寻找预防沙门氏菌病的新方法，因为有特征性的碳水化合物结构。在沙门氏菌表面，在这个项目中，成立了一个协作团队来开发有效的基于碳水化合物的抗沙门氏菌疫苗。在目标 1 中，不依赖从病原菌中分离出的碳水化合物，将开发合成策略以生产结构明确的沙门氏菌聚糖在目标 2 中，沙门氏菌聚糖将与类似病毒结合。颗粒、噬菌体 Qβ 作为针对特定致病性沙门氏菌的潜在疫苗 Qβ 聚糖缀合物的有希望的初步结果支持了这一点。能够诱导高滴度（兔子体内超过 8000 万 ELISA 单位）和持久的抗聚糖 IgG 抗体，可以为小鼠提供全面的保护，使其免受致命的挑战基于这些结果，Qβ 载体将被改造以增强其作用。目标 3 是一种广谱抗沙门氏菌免疫反应的能力。将开发沙门氏菌疫苗，可针对多种疾病提供强有力的保护通过单一疫苗来识别主要致病性沙门氏菌，可以很好地补充菌株。这项工作可以为抗沙门氏菌疫苗带来令人兴奋的新方向。的发展，为对抗沙门氏菌病提供了急需的新武器。