Using a computational design methodology, SARS-CoV-2 spike proteins containing engineered amino acid changes to the receptor binding domain (RBD) were designed. These engineered spike proteins improved the immune response upon immunization of animals. An engineered RBD was also expressed at greater yield, had increased temperature stability, and improved the immune response upon immunization of animals. Specifically, the disclosed RBD designs can be produced approximately 7 times more efficiently than the native sequence, facilitating vaccine manufacturing on a global scale. The disclosed designs also have up to 10 °C higher thermal stability than the native sequence, suggesting enhanced stability during storage and when in the body. Finally, immunization of animals with the disclosed antigens produces up to 10-fold higher levels of blocking antibodies than the native sequence and 30-fold higher levels of pseudoviral neutralizing antibodies. An additional RBD protein has been engineered to eliminate the need for glycosylation, facilitating production and single-component nanoparticle display of the antigen. The engineered receptor binding domain (RBD) and spike protein antigens produce significant improvements in pre-clinical animal models and may be used to develop improved coronavirus vaccines.
This technology is available for licensing for commercial development in accordance with 35 U.S.C. 209 and 37 CFR Part 404, as well as for further development and evaluation under a research collaboration.
- Novel SARS-CoV-2 vaccine.
- Improved SARS-CoV-2 diagnostics using stabilized antigens.
- Method of designing vaccine candidates or stabilized antigens by computational. optimization of amino acid identity, followed by additional sequence comparison and selection (Stabilizer for Protein Expression and Epitope Design (SPEEDesign)).
- Novel SARS-CoV-2 spike vaccine with improved breadth and duration of protection.
- Novel RBD monomer and nanoparticle designs that are more immunogenic and stable than the naturally occurring RBD sequence.
- Computational method of designing vaccine antigens.