Thermostabilized Subunit Glycoprotein Vaccine Platform: Immune Characterization of an Emulsified Adjuvant with SARS-CoV-2 Spike Protein and EBOV GP

7. Project Summary/Abstract The proposal requests funding to support manufacturing and immune characterization of a novel, emulsified adjuvant which is uniquely compatible with lyophilization strategies to enable thermostabilization of glycoprotein vaccines. The major objectives of the study are to transfer and optimize the manufacture of a novel adjuvant and to characterize and assess the comparative immunogenicity of different adjuvant formulations in terms of both humoral and cell mediated immunity, utilizing two different multimeric glycoprotein antigens. Ultimately, this program will identify an optimal adjuvant formulation, capable of potentiating both humoral and cell mediated immunity to protein antigens, compatible with lyophilization and resulting in a thermostabilized vaccine utilizing Generally Regarded as Safe (‘GRAS’) excipients. Specific formulation development will be done in the context of the Zaire ebolavirus (EBOV) GP, a component of our trivalent filovirus vaccine (TriFiloVax) targeting EBOV, Sudan ebolavirus (SUDV) and marburgvirus (MARV) and with SAR-CoV-2 spike protein, supporting COVID-19 vaccine development efforts. While state of the art medical treatment may increase the chances of survival of both the highly fatal EBOV and the highly transmissible COVID-19, currently no antiviral therapy is available to prevent or cure the disease. Vaccination remains the most feasible route for addressing and preventing future epidemics. Ongoing clinical development in the context of EBOV has identified both therapeutics and vaccines which are being tested in the ongoing outbreak in the Democratic Republic of Congo. However, these approaches are highly selective for EBOV only. The sole approved vaccine is a virally vectored vaccine requiring cold storage (lt-60°C) storage / distribution and also cannot be used in at-risk populations showing any signs of immunodeficiency or in pregnant women and is potentially more variable in less responsive populations. These vaccine platforms also may not be used repeatedly (either as boosters or with other protein antigens) because of the humoral induced immunity to the viral platform which occurs with vaccination. There is no vaccine for MARV, SUDV or COVID-19. In contrast, subunit vaccines offer many advantages, including improved safety, compatibility with immunosuppressed, immunocompromised or high risk populations or those who have previously received virally vectored vaccines. Thermostabilized formulations also facilitate stockpiling and emergency use in logistically challenging environments. The specific aims of the proposal include to i) transfer manufacturing methods and manufacture engineering lots of CoVaccine with varying Polysorbate 80 content and ii) characterize the enhancement of both humoral and cell mediated immunity by CoVaccine HT™ with SARS-CoV-2 Spike protein and EBOV GP, thereby facilitating the development of TriFiloVax (for EBOV, MARV and SUDV) and CiVax (for COVID-19) and more generally for other protein vaccines.