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

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。为了响应RFA-13-179，印度-美国疫苗行动计划小型研究资助计划(R03)，美国和印度的两个糖学小组组成了一个合作团队，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，从主要致病血清中生产结构明确的沙门氏菌相关多糖，而不是依赖于从病原菌中分离出多糖。这些多糖将与一种类似病毒的颗粒--噬菌体Q？通过最先进的生物偶联化学。在目标2中，将评估针对这些糖结合物的体液免疫反应。像病毒一样的粒子Q？能以高度组织化的方式展示糖类抗原并诱导强大的辅助性T细胞激活，预计Q？结合物能显著增强沙门氏菌相关糖蛋白的免疫球蛋白G抗体应答，并产生糖链特异性免疫记忆。疫苗构建体抵御致命沙门氏菌攻击的能力将被确立。这项工作可以为抗沙门氏菌疫苗的开发带来一个令人兴奋的新方向。

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.