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

新型疫苗平台的开发：表面抗原/佐剂疫苗工程（SAAVE）

• 批准号: 9899172
• 负责人: Michael Stephen Trent
• 金额: $ 74.97万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-22 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9899172
• 关键词: Adjuvant; Antibody titer measurement; Antigen Targeting; Antigens; Bacteria; Benchmarking; Cell Culture Techniques; Cessation of life; Clinical; Communicable Diseases; Data; Development; Diphtheria; Disease; Emulsions; Engineering; Escherichia coli; Exhibits; Ferrets; Fever; Future; Generations; Glycoconjugates; Glycolipids; Human; Hydrophobicity; Immune response; Immunity; Infection; Inflammatory; Inflammatory Response; Influenza; Influenza A virus; Influenza Hemagglutinin; Innate Immune System; Laboratories; Libraries; Ligands; Lipid A; Lipopolysaccharides; Longevity; Measurement; Membrane; Methods; Mind; Modeling; Modernization; Mus; Nature; Personal Satisfaction; Poison; Poliomyelitis; Population; Process; Production; Proteins; Public Health; Recombinant DNA; Recording of previous events; Reporting; Signal Transduction; Smallpox; Structure; Surface; Surface Antigens; Symptoms; System; TLR4 gene; Technology; Testing; Tetanus; United States Food and Drug Administration; Update; Vaccinated; Vaccination; Vaccine Design; Vaccine Production; Vaccines; Variant; Vesicle; Virus; base; combat; combinatorial; cost effective; cytokine; design; efficacy testing; egg; improved; in vivo; influenza epidemic; influenza outbreak; influenza virus vaccine; influenzavirus; innovation; microorganism; multi-drug resistant pathogen; new technology; novel vaccines; pandemic disease; pandemic influenza; prevent; protein purification; public health intervention; receptor; seasonal influenza; stem; success; tool; universal influenza vaccine; universal vaccine; vaccine candidate; vaccine delivery; vaccine development; vaccinology

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.

抽象的 疫苗接种也许是人类历史上最有效的公共卫生干预措施。过去的事 200年来，疫苗研发取得了许多成就，成功战胜了疾病 例如天花、脊髓灰质炎、破伤风、白喉等。然而，对新产品的需求不断增长 对抗难以针对的疾病的疫苗技术。此外，疫苗接种可能是唯一的方法 预防多重耐药病原体引起的传染病的行动方针。初级 当前应用程序的目标是开发一个疫苗平台，允许显示两者 非致病性大肠杆菌表面的工程抗原和佐剂。该平台允许使用 全细菌和外膜囊泡（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、高性价比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球范围内造成数百万例严重感染病例，并导致 不受控制的流感大流行可能导致数千万人死亡。最有效的方法是 通过疫苗接种来保护人们免受流感的侵害；然而，目前的流感疫苗并不 具有广泛的保护性，并且必须每年进行更新，这是一个低效、昂贵且费力的过程。我们的新 抗原/佐剂细菌展示平台有可能克服这些弱点。具体 该提案的目的是（i）改造大肠杆菌的细菌表面以展示目标抗原和 保护性疫苗的佐剂，(ii) 设计多价流感疫苗的生产 异亚型免疫，以及（iii）测试我们的工程诱导的保护的功效和持久性 雪貂通用流感疫苗。