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采用新型生物工程纳米颗粒，盐古菌气囊泡（HGV）作为佐剂和抗原递送系统，价格低廉，有效，货架稳定（无需冷藏）。当 当将具有表面展示抗原的HGV纳米颗粒施用于动物时，产生强烈的长寿命免疫应答。在以前的工作中，来自细菌和病毒病原体的抗原表达为与HGV蛋白组分之一的融合物，并且在所有情况下，重组HGV在小鼠中具有高度免疫原性。我们计划测试HGV作为疫苗载体对抗伤寒沙门氏菌（伤寒的病原体）的有效性。这些人类病原体仍然是许多国家发病率和死亡率的重要原因，因为卫生条件差，水和食物被人类粪便污染。我们的目标是开发一种安全、廉价的口服疫苗，以对抗侵袭性沙门氏菌疾病，这种疫苗可用于发展中国家和发达国家。我们建议：（a）产生在HGV纳米颗粒上展示的多种沙门氏菌保护性抗原;和（B）递送生物工程化的HGV-疫苗抗原纳米颗粒并确定它们在小鼠模型中的保护效力。我们还将进行更深入的免疫学分析，并使用HGV制剂的组合测试保护。这些研究将为随后在人类中评估这种方法奠定基础，并定制用于预防其他疾病的系统。开发一种安全、廉价、有效和货架稳定的口服佐剂和疫苗运载工具将导致预防传染病的全球革命。

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.