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: 8823965
• 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/8823965
• 关键词: Abbreviations; Alkynes; Amides; Antibody Response; Antigens; Azides; Bacteria; Bacteriophages; Bone Marrow; Bovine Serum Albumin; CD4 Positive T Lymphocytes; Carbohydrates; Cell surface; Characteristics; Chemistry; Clinic; Copper; CpG dinucleotide; Dendritic Cells; Development; Disease; Dose; Enzyme-Linked Immunosorbent Assay; Enzymes; Esters; Galactose; Glycoconjugates; Granulocyte-Macrophage Colony-Stimulating Factor; Helper-Inducer T-Lymphocyte; Horseradish Peroxidase; Immune response; Immunoglobulin G; Immunologic Memory; Immunology; Immunosorbents; India; Interleukin-4; Investigation; Keyhole Limpet Hemocyanin; Lead; Length; Link; Lipid A; Lipopolysaccharides; Mannose; Multi-Drug Resistance; Mus; Oligosaccharides; Pattern; Polysaccharides; Public Health; Reaction; Receptors, Antigen, B-Cell; Research; Research Project Grants; Resort; Rhamnose; Route; Salmonella; Salmonella Vaccines; Salmonella enteritidis; Salmonella infections; Salmonella paratyphi; Salmonella typhi; Salmonella typhimurium; Spottings; Structure; Synthesis Chemistry; T-Cell Activation; Tetanus Toxoid; Time; Toll-like receptors; Tumor-Associated Carbohydrate Antigens; Typhoid Fever; Ursidae Family; Vaccination; Vaccine Adjuvant; Vaccines; Vi capsular polysaccharide; Virus-like particle; Work; base; carboxyfluorescein; combat; cycloaddition; design; enzyme linked immunospot assay; man; novel; novel vaccines; pathogenic bacteria; prevent; programs; public health relevance; 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 Q? 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 Q? can display the carbohydrate antigens in a highly organized manner and elicit powerful helper T cell activation, it is expected that Q? 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）是全世界的一个主要公共卫生问题。作为对RFA-13-179的回应。疫苗行动计划小额研究资助计划（R03），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，从主要致病血清型中生产结构明确的沙门氏菌相关聚糖，而不是依赖于从致病性细菌中分离多糖。这些聚糖将与一种类似病毒的粒子结合，噬菌体Q？通过最先进的生物偶联化学。在目标2中，将评估针对这些糖缀合物的体液免疫反应。像粒子Q一样的病毒？能够以高度有组织的方式显示碳水化合物抗原并引发强大的辅助T细胞激活，预计Q？结合物可以显著增强针对沙门氏菌相关聚糖的IgG抗体反应，并产生聚糖特异性免疫记忆。构建的疫苗抵御致命沙门氏菌挑战的能力将得到证实。这项工作可以为抗沙门氏菌疫苗的开发开辟一个令人兴奋的新方向。