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。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。这些聚糖将通过最先进的生物偶联化学与病毒样颗粒噬菌体Qß偶联。在目标2中，将评估针对这些糖缀合物的体液免疫反应。由于病毒样颗粒Qß可以高度有序地显示碳水化合物抗原，并引发强大的辅助T细胞活化，因此Qß缀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。

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.