Glycoconjugate Nanoparticle Vaccines Against Burkholderia Infections

摘要马来伯克霍尔德氏菌和假腮腺炎伯克霍尔德氏菌是扁桃体和扁桃体的致病菌和病原体。 类鼻疽病。目前，还没有有效的预防扁桃体肿块或恶臭的疫苗。 发展起来的。然而，伯克霍尔德氏菌疫苗的开发重新引起了人们的关注。 因为病原体似乎是恶意用作生物武器的理想特征。 此外，疫苗对高危人群的免疫接种也将具有重要价值。 类鼻疽病/腺病是世界上流行的地区。因此，我们的长期目标是开发一个 允许高效地产生能够预防两种腺体的多组分疫苗 和类鼻疽病。我们的方法将使用偶联到金纳米颗粒(NP)上的糖偶联物并测试它们的 临床相关感染模型的保护性。测试的中心假说表明 与NP多糖偶联的马来或假单胞菌蛋白抗原可诱导相应的免疫保护作用 这些抗原将与临床上重要的血清学/免疫学相关 读数。这一假说将通过开发不同的蛋白质-多糖NPs和比较 它们在体内的功效。灵活的NP平台将允许我们另外结合已识别的新抗原 被其他团体视为进一步加强保护性免疫。我们将建立一个最佳的免疫程序 并在临床相关和高度可控的气雾剂中测试蛋白质-多糖纳米粒的有效性 小鼠感染模型。最后，我们的目标是确定蛋白质诱导的保护相关/生物标记物- 多糖NP疫苗接种。这一建议是创新的，因为它利用了亚单位NP的使用 疫苗，由于其较低的成本和更广泛的传播疫苗，可以很容易地获得许可 针对高危人群。总而言之，这些结果将帮助我们确定蛋白质保护作用的相关性- 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.