Development of a novel vaccine platform: Surface Antigen/Adjuvant Vaccine Engineering (SAAVE)

摘要 疫苗接种可能是人类历史上最有效的公共卫生干预措施。过去 200年来，疫苗开发取得了许多成就，成功地对抗了疾病， 如天花、小儿麻痹症、破伤风、白喉等。然而，对新的 疫苗技术来对抗难以瞄准的疾病。此外，疫苗接种可能是唯一的 采取行动，预防由多重耐药病原体引起的传染病。主 本申请的目的是开发一种疫苗平台， 非致病性E.杆菌该平台允许使用 全菌和外膜囊泡（OMV）作为疫苗生产和疫苗递送系统。 在目前的应用中，这一创新、高效、性价比高的疫苗平台将直接应用于 生产具有广泛保护性的通用流感疫苗。 季节性流感流行每年在全世界造成数百万例严重感染， 如果流感大流行得不到控制，可能会导致数千万人死亡。的最有效方法 保护人群免受流感是通过接种疫苗;然而，目前的流感疫苗不是 广泛的保护性，并且必须每年更新，这是一个低效、昂贵和费力的过程。我们的新 抗原/佐剂细菌展示平台具有克服这些弱点的潜力。具体 本研究的目的是（i）对大肠杆菌的表面进行工程改造;用于展示靶向抗原的大肠杆菌， 保护性疫苗的佐剂，（ii）设计生产多价流感疫苗， 异亚型免疫，和（iii）测试我们的工程化的免疫诱导的保护的功效和持久性。 雪貂的通用流感疫苗。

Abstract Vaccination is perhaps the most effective public health intervention in the history of mankind. Over the past 200 years, there have been many accomplishments in vaccine development with successes against diseases such as smallpox, polio, tetanus, diphtheria, and others. However, there is an ever-growing need for new vaccine technologies to combat diseases that are difficult to target. Furthermore, vaccination may be the only course of action to prevent infectious diseases caused by multi-drug resistant pathogens. The primary objective of the current application is to develop a vaccine platform that allows for the display of both engineered antigens and adjuvants on the surface of non-pathogenic E. coli. This platform permits the use of whole bacteria and outer membrane vesicles (OMVs) as both vaccine production and vaccine delivery systems. In the current application, this innovative, efficient, and cost-effective vaccine platform will be directly applied to the production of a broadly protective, universal influenza vaccine. Seasonal influenza epidemics cause millions of cases of severe infection per year worldwide and an uncontrolled influenza pandemic could result in the death of tens of millions. The most effective approach to protecting the population from influenza is through vaccination; however, current influenza vaccines are not broadly protective and must be updated yearly in an inefficient, expensive, and laborious process. Our new antigen/adjuvant bacterial display platform has the potential to overcome these weaknesses. The Specific Aims of this proposal are (i) to engineer the bacterial surface of E. coli for display of targeted antigens and adjuvants for protective vaccines, (ii) to engineer the production of polyvalent influenza vaccine offering heterosubtypic immunity, and (iii) to test the efficacy and durability of protection induced by our engineered universal influenza vaccines in ferrets.