A Bioengineerable Self-Adjuvating Nanoparticle for Antigen Delivery

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). Whenadministered 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. <p/>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. <p/>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.