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

• 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
• 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

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)是全世界的主要公共卫生问题。 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。因为有独特的碳水化合物结构 在沙门氏菌表面，在这个项目中，成立了一个合作团队来开发 有效的碳水化合物抗沙门氏菌疫苗。 在目标1中，不是依赖于从病原菌中分离出来的碳水化合物， 将开发合成策略来生产结构明确的沙门氏菌糖链 主要致病血清型。在AIM 2中，糖链沙门氏菌将与一种类似于 颗粒，噬菌体Qβ作为针对特定致病沙门氏菌的潜在疫苗 菌株。这一点得到了有希望的初步结果的支持，即Qβ多糖结合物是 能够诱导高滴度(在兔体内超过8000万个酶联免疫吸附试验单位)和持久的抗葡聚糖免疫球蛋白 抗体，可通过以下方式为小鼠提供完全保护，使其免受致命攻击 沙门氏菌。在这些结果的基础上，Qβ航母将被设计成增强其 进一步增强抗沙门氏菌免疫反应的能力。在《目标3》中，一种广谱反病毒 将开发沙门氏菌疫苗，这种疫苗可以提供强大的保护，防止多重 主要致病沙门氏菌的种类由单一疫苗接种。这可以很好地补充菌株 特定的疫苗。这项工作可以为抗沙门氏菌疫苗带来一个令人兴奋的新方向 发展，为抗击沙门氏菌病提供了亟需的新武器库。