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Kathryn Loeffler
BioE PhD Proposal Presentation
Time and Date: 3 PM, Monday, November 7th, 2022
Location: IBB 1128
Virtual Link: https://gatech.zoom.us/j/98227695462?pwd=d3luUmxxVTVlN0NWazN6Y3Jsczc2UT09
Advisor: Ravi Kane, Ph.D. (Chemical and Biomolecular Engineering)
Committee Members:
John Blazeck, Ph.D. (Chemical and Biomolecular Engineering)
Julie Champion, Ph.D. (Chemical and Biomolecular Engineering)
M.G. Finn, Ph.D. (Chemistry and Biochemistry)
Mark Prausnitz, Ph.D. (Chemical and Biomolecular Engineering)
Designing VLP-based Vaccines for Broad Protection Against Coronaviruses and Influenza
The design of vaccines that provide broad protection against highly variable viruses such as influenza and coronaviruses poses a significant challenge. Current vaccination methods and natural infection elicit an immune response directed towards variable areas of the virus leading to a narrow response that does not protect against re-infection by similar strains or variants. A vaccine that can provide protection against a broad range of influenza viruses or coronaviruses would be ideal in this situation.
In our vaccine constructs, we display the influenza surface glycoprotein hemagglutinin (HA) or the coronavirus spike (S) protein (or its subunits) on the surface of virus-like particles (VLPs). We have focused on these proteins due to their critical role in viral attachment and entry into host cells. We have chosen to use VLPs as they are attractive scaffolds for the multivalent display of protein antigens. We have developed and are currently working on several vaccine constructs.
In Aim 1, we developed a vaccine based on the receptor binding domain (RBD) of S, which is the target of many neutralizing antibodies. We have shown that VLPs displaying RBD induce a potent neutralizing response against several SARS-CoV-2 variants. In Aim 2, we are developing a cocktail vaccine containing S proteins from various sarbevoviruses that we expect to elicit a broadly protective antibody response. In Aim 3, we use the S2 domain, a highly conserved region of the S protein, as the antigen in our vaccine. We have shown that this vaccine construct elicits cross-reactive antibodies and provides protection against several SARS-CoV-2 variants as well as a pangolin CoV. In Aim 4, we propose to test whether controlling the orientation of the S and HA proteins on the surface of a VLP will enhance the antibody response to conserved regions of these proteins. For all of these vaccine constructs, we will assess their efficacy in an animal model, including measuring endpoint and neutralization titers and challenging with relevant sarbecoviruses and influenza viruses.
