Glycoconjugate Nanoparticle Vaccines Against Burkholderia Infections

鼻疽伯克霍尔德氏菌和B。假鼻疽是细菌病原体和鼻疽的病原体， 类鼻疽。目前，用于预防鼻疽或鼻疽病的有效疫苗还没有开发出来。 开发然而，伯克霍尔德氏菌疫苗的开发重新受到关注 因为这些病原体看起来很适合被恶意用作生物战武器。 此外，疫苗还将对高危人群的免疫接种具有重要价值， 类鼻疽病/鼻疽流行区。因此，我们的长期目标是开发一个平台， 允许有效地产生多组分疫苗 和类鼻疽。我们的方法将使用与金纳米颗粒（NP）偶联的糖缀合物，并测试其 在临床相关感染模型中的保护特性。检验的中心假设表明， B蛋白抗原。鼻疽或B。与NP多糖偶联的类鼻疽杆菌将引起相关的免疫保护作用。 这些抗原将与临床上重要的血清学/免疫学 读数该假设将通过开发不同的蛋白质-多糖纳米粒并比较 其在体内的功效。灵活的NP平台将使我们能够额外纳入新的抗原鉴定 进一步增强保护性免疫力。我们将建立一个最佳的免疫程序 并测试蛋白质-多糖NP在临床相关和高度受控的气雾剂中的功效 感染的小鼠模型。最后，我们的目标是确定蛋白质诱导的保护作用的相关物/生物标志物， 多糖NP疫苗接种。这个建议是创新的，因为它利用了一个子单位-NP的使用 疫苗，由于其成本较低，接种范围更广， 针对高危人群。总之，这些结果将帮助我们确定蛋白质保护的相关性- 多糖纳米颗粒，并提供优化的疫苗接种策略。

Burkholderia mallei and B. pseudomallei are bacterial pathogens and causative agents of glanders and melioidosis, respectively. At present, effective vaccines for prevention of glanders or meliodosis have not been developed. However, renewed attention has been directed toward development of Burkholderia vaccines because of the pathogens' seemingly ideal characteristics for malicious use as a biowarfare weapon. Additionally, a vaccine will also have significant value for the immunization of at-risk populations in melioidosis/glanders endemic areas of the world. Therefore, our long-term goal is to develop a platform that allows for the efficient generation of a multicomponent vaccine which is able to protect against both glanders and melioidosis. Our approach will use glycoconjugates coupled to gold nanoparticles (NP) and test their protective properties in clinically relevant models of infection. The central hypothesis tested indicates that protein antigens of B. mallei or B. pseudomallei coupled to NP polysaccharides will elicit protection in relevant mammalian species, and that these antigens will correlate with clinically important serologic/immunologic readouts. The hypothesis will be evaluated by developing different protein-polysaccharide NPs and comparing their efficacy in vivo. The flexible NP platform will allow us to additionally incorporate novel antigens identified by other groups as further enhancing protective immunity. We will establish an optimal immunization procedure and test the efficacies of protein-polysaccharide NPs in a clinically relevant and highly controlled aerosol murine model of infection. Finally, we aim to identify the correlates/biomarkers of protection induced by protein- polysaccharide NP vaccination. This proposal is innovative because it capitalizes on the use of a subunit-NP vaccine, which could be easily licensable because of its lower cost and more widely disseminated vaccinations for at-risk populations. Together, these outcomes will help us to identify correlates of protection from protein- polysaccharide nanoparticles and provide optimized vaccination strategies.