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

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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.