BioE PhD Defense Presentation- Kathryn Loeffler
Advisor:
Dr. Ravi Kane (Chemical and Biomolecular Engineering)
Committee:
Dr. John Blazeck (Chemical and Biomolecular Engineering)
Dr. Julie Champion (Chemical and Biomolecular Engineering)
Dr. MG Finn (Chemistry and Biochemistry)
Dr. Mark Prausnitz (Chemical and Biomolecular Engineering)
Designing Protein-based Vaccines for Broad Protection Against Coronaviruses and Influenza
Vaccination is one of the most effective methods of reducing or preventing infectious diseases. A significant remaining challenge is the design of vaccines for long-lasting and broadly protective immunity against highly variable viruses. Many viruses mutate quickly to escape host immune systems, leading to diverse strains with variable surface proteins. The immune response to one of these viruses focuses on the immunodominant but variable regions, which results in a strain-specific response. It is desirable to instead redirect the immune response to conserved areas of viral proteins, producing an immune response that can recognize and effectively eliminate many strains.
In this work, we have developed recombinant proteins vaccines with the goal of eliciting broadly protective immune responses. We found that the highly immunogenic SARS-CoV-2 receptor binding domain elicits high titers of neutralizing antibodies against SARS-CoV-2 variants, while the more conserved S2 subunit elicits non-neutralizing though still protective immunity against SARS-CoV-2 and closely related viruses. The S proteins of SARS-CoV-2 and related CoVs can be combined into a cocktail vaccine to elicit neutralizing and broadly protective antibodies against clade 1 viruses. Lastly, we demonstrated that long-lasting immunity can be elicited by VLP-based HA vaccines. Together, the results of these different strategies may aid in the design of broadly protective vaccines.