A Bioengineerable Self-adjuvating Nanoparticle for Antigen Delivery

描述(由申请人提供)：一种独特的疫苗平台使用新型可生物工程纳米颗粒--嗜盐古菌气泡(HGV)--作为佐剂和抗原递送系统，该系统廉价、有效且货架稳定(不需要冷藏)。什么时候 给动物注射HGV纳米颗粒和表面展示的抗原，可以产生强大的长寿免疫反应。在以前的工作中，来自细菌和病毒病原体的抗原被表达为与HGV蛋白组分之一的融合，并且在所有情况下，重组HGV在小鼠中都具有高度的免疫原性。我们计划测试HGV作为疫苗载体对抗伤寒沙门氏菌的有效性。伤寒是伤寒的病原体。这些人类病原体仍然是许多国家发病和死亡的重要原因，原因是卫生条件差，水和食物受到人类排泄物的污染。我们的目标是朝着开发一种安全、廉价的口服疫苗的方向迈进，以对抗侵袭性沙门氏菌病，这种疫苗既可以在发展中国家使用，也可以在发达国家使用。我们建议：(A)生产展示在HGV纳米颗粒上的多个沙门氏菌保护性抗原；以及(B)传递生物工程HGV疫苗抗原纳米颗粒，并在小鼠模型中测定其保护效果。我们还将进行更深入的免疫学分析，并使用HGV配方组合进行保护试验。这些研究将为随后对这种方法在人类身上的评估奠定基础，并为预防其他疾病定制系统。开发一种廉价、有效和货架稳定的安全、口服佐剂和疫苗递送工具，应该会在预防传染病方面引发一场全球革命。

DESCRIPTION (provided by applicant): A unique vaccine platform employs novel bioengineerable nanoparticles, Haloarchaeal gas vesicles (HGVs), as an adjuvant and antigen delivery system that is inexpensive, effective, and shelf-stable (requiring no refrigeration). When administered to animals, HGV nanoparticles with surface-displayed antigens produce strong long-lived immune responses. In previous work, antigens from bacterial and viral pathogens were expressed as a fusion to one of the HGV protein components and in all cases the recombinant HGVs were highly immunogenic in mice. We plan to test the effectiveness of HGVs as a vaccine vehicle against Salmonella enterica serovar Typhi, the causative agent of typhoid fever. These human pathogens remain important causes of morbidity and mortality in many countries as a result of poor sanitation, and water and food contaminated by human fecal waste. Our goal is to progress toward the development of a safe and inexpensive oral vaccine against invasive Salmonella disease that can be used in both the developing and developed world. We propose to: (a) produce multiple Salmonella protective antigens displayed on HGV nanoparticles; and (b) deliver the bioengineered HGV-vaccine antigen nanoparticles and determine their protective efficacy in a mouse model. We will also perform more in-depth immunological analyses and test protection using combinations of HGV formulations. These studies will lay the foundation for subsequent evaluation of this approach in humans as well as customize the system for prevention of other diseases. The development of a safe, oral adjuvant and vaccine delivery vehicle which is inexpensive, effective, and shelf-stable should lead to a global revolution in the prevention of infectious diseases.