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.

摘要