Sydney Wimberley

BioE PhD Defense Presentation

Time and Date: 10:00 am August 28,

Location: EBB 5029

Zoom link: https://gatech.zoom.us/my/sydwim

Advisor: Julie Champion, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Tech)

Committee Members:  

John Blazeck, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Tech)

Vida Jamali, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Tech)

Manu Platt, Ph.D. (NIH|NBIB, Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech)

Mark Prausnitz, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Tech)

Engineering protein nanocages for Influenza and Chlamydia Vaccines

Recombinant protein subunit vaccines overcome challenges faced by traditional whole pathogen vaccines, including preservation of antigen structure and directing both a humoral and a cellular immune response towards specific epitopes. However, the immune system has evolved to recognize highly repetitive antigens presented on pathogen surfaces, not soluble antigens. To induce robust immune responses, antigen display platforms have been designed to mimic pathogen antigen display. There are many different types of protein antigen displays, such as crosslinked nanoparticles and de novo self-assembling proteins. This thesis explores the use of self-assembled protein nanocages (SAPN) to improve humoral immune responses for a universal influenza vaccine and to develop and evaluate a Chlamydia vaccine. SAPNs are comprised of coil peptides that self-assemble into a cage. For vaccine SAPNs, fusion proteins were made of coiled coils and antigens. For influenza and Chlamydia SAPNs, combinations of antigens from the pathogens were showcased on the outside or the inside of the cage. The SAPNs were used to investigate antigen display and the factors that can affect immune responses, including accessibility and selection. This includes how a glycine linker can improve accessibility of a small antigen on the cage to induce a significant humoral response, and how selection of antigens may have a greater impact on immune responses than display. Overall, this thesis demonstrates the modular nature of  SAPNs with the ability to display both viral and bacterial antigens.