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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：
10653943
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 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10653943
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 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 Vaccines Vertebral column Virus-like particle Work capsule carbohydrate structure combat design enteritis fighting immunogenic immunogenicity non-typhoidal Salmonella 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）是一个主要的公共卫生问题，世界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，一个合作小组成立，有效的碳水化合物抗沙门氏菌疫苗。在aim 1中，将开发合成策略，以生产结构明确的沙门氏菌聚糖，主要致病血清型。在目标2中，沙门氏菌聚糖将与病毒样噬菌体Qβ作为特异性沙门氏菌疫苗的研究进展菌株这得到了有希望的初步结果的支持，即Qβ聚糖缀合物是能够诱导高滴度（在兔中超过8000万ELISA单位）和持久的抗聚糖IgG 抗体，它可以提供完全保护小鼠免受致命的挑战，沙门氏菌。在这些结果的基础上，Qβ载体将被设计成增强其进一步增强抗沙门氏菌免疫反应的能力。在aim 3中，广谱抗- 沙门氏菌疫苗将被开发出来，它可以提供强大的保护，主要致病性沙门氏菌的种类。这可以很好地补充菌株特定疫苗。这项工作可以为抗沙门氏菌疫苗带来令人兴奋的新方向发展，提供了一个急需的新的武器库，在打击沙门氏菌病。