Virus like particles as carriers for carbohydrate based anti-Salmonella vaccines

病毒样颗粒作为碳水化合物抗沙门氏菌疫苗的载体

• 批准号: 9118056
• 负责人: Xuefei Huang
• 金额: $ 7.68万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9118056
• 关键词: Alkynes; Amides; Antibody Response; Antigens; Azides; Bacteria; Bacteriophages; CD4 Positive T Lymphocytes; Carbohydrates; Cell surface; Characteristics; Chemistry; Clinic; Copper; Development; Disease; Dose; Glycoconjugates; Health; Helper-Inducer T-Lymphocyte; Immune response; Immunoglobulin G; Immunologic Memory; Immunology; India; Investigation; Lead; Length; Multi-Drug Resistance; Mus; Oligosaccharides; Pattern; Polysaccharides; Public Health; Reaction; Research Project Grants; Resort; Route; Salmonella; Salmonella Vaccines; Salmonella enteritidis; Salmonella infections; Salmonella typhi; Salmonella typhimurium; Structure; Synthesis Chemistry; T-Cell Activation; Time; Tumor-Associated Carbohydrate Antigens; Typhoid Fever; Ursidae Family; Vaccination; Vaccine Adjuvant; Vaccines; Vi capsular polysaccharide; Virus-like particle; Work; base; combat; cycloaddition; design; novel; novel vaccines; pathogenic bacteria; prevent; programs; resistant strain; response; vaccine development

DESCRIPTION: Salmonella infections (salmonellosis) are a major public health problem throughout the world. In response to RFA-13-179, Indo-U.S. Vaccine Action Program Small Research Grant Program (R03), a collaborative team is formed between two glycoscience groups in the US and India to develop carbohydrate based anti-Salmonella vaccines. Instead of relying on isolating polysaccharides from the pathogenic bacteria, in aim 1, synthetic strategies will be developed to produce structure well defined Salmonella associated glycans from major pathogenic serovars. These glycans will be conjugated with a virus like particle, bacteriophage Qß via state of the art bioconjugation chemistry. In aim 2, the humoral immune responses against these glycoconjugates will be evaluated. As the virus like particle Qß can display the carbohydrate antigens in a highly organized manner and elicit powerful helper T cell activation, it is expected that Qß conjugates can significantly boost the IgG antibody responses against the Salmonella associate glycans and generate glycan specific immunological memory. The abilities of the vaccine constructs to protect against lethal Salmonella challenge will be established. This work can lead to an exciting new direction for anti-Salmonella vaccine development.

描述：沙门氏菌感染（沙门氏菌病）是一个主要的公共卫生问题在世界各地。为响应RFA-13-179，印度-美国疫苗行动计划小额研究资助计划（R 03），美国和印度的两个糖科学小组组成了一个合作小组，以开发基于碳水化合物的抗沙门氏菌疫苗。在目标1中，将开发合成策略以从主要致病血清型产生结构明确的沙门氏菌相关聚糖，而不是依赖于从致病细菌中分离多糖。这些聚糖将通过最先进的生物偶联化学与病毒样颗粒、噬菌体Q101偶联。在目标2中，将评价针对这些糖缀合物的体液免疫应答。由于病毒样颗粒QALG可以以高度组织化的方式展示碳水化合物抗原并引发强大的辅助T细胞活化，因此预期QALG缀合物可以显著增强针对沙门氏菌相关聚糖的IgG抗体应答并产生聚糖特异性免疫记忆。将确定疫苗构建体保护免受致死性沙门氏菌攻击的能力。这项工作可以为抗沙门氏菌疫苗的开发带来令人兴奋的新方向。