Glycoengineered Vesicle Vaccine Against Bacterial Pathogens
Vaccines are undoubtedly one of the greatest medical successes in human history, saving countless lives and billions of dollars through preventative medicine. Diseases such as measles, polio and smallpox have all been but eradicated. However, previous approaches to vaccine development using live attenuated or inactivated pathogens have stalled against pathogens with more sophisticated pathogenesis or are difficult to culture at a large scale. Whereas early approaches to vaccination sought to use whole organisms, and current approaches focus on the design of synthetic particles, our work seeks to harness the ability of Escherichia coli as a recombinant expression platform and its ability to produce nanoscale outer membrane vesicles (OMVs) as an all-in-one vaccine delivery system in vivo. Outer membrane vesicles (OMVs) have been shown to deliver recombinant protein antigens along with immunostimulatory components in a naturally produced liposome that closely mimics live pathogens. In this work, we have engineered E. coli OMVs to recombinantly display pathogenic carbohydrate structures bacterial pathogens such as Neisseria meningitidis and Francisella tularensis as well as the tumor-associated T antigen. These glycoengineered OMVs (glycOMVs) have shown to elicit a robust adaptive immune response in vaccinated mice as indicate by a significant increase in production of carbohydrate-specific antibodies. Furthermore, we have been able to demonstrate that vaccination with F. tularensis OMVs confers protection in mice against subsequent infection by the pathogen. These experiments serve as a proof-of-concept model that highlights the versatility of OMVs as a novel vaccine platform.
Outer membrane vesicles; Glycobiology; Immunology
Chang,Yung-Fu; Putnam,David A.
Ph. D., Chemical Engineering
Doctor of Philosophy
dissertation or thesis