Promising Tools for SARS-CoV2 (COVID-19) Vaccine and Diagnostic Test Development: Stabilizing Mutants of Prefusion Spike Protein and Improved Yeast Surface Display Engineering Platform

Background

Spike protein is a major antigenic determinant of COVID-19 and binds to host cell membranes in an “up” conformation. Engineered Spike proteins in the “up” conformation would be valuable in serological diagnostic test and vaccine development, as many of the SARS-CoV-2 neutralizing antibodies selectively recognize the Spike “up” conformation. Stabilized “up” conformation engineered Spike proteins are already being used in Phase I vaccine clinical trials.

Technology

Researchers from the Whitehead Lab at CU Boulder have identified additional mutations that further stabilize the SARS-CoV-2 Spike protein in its ”up” conformation. These engineered Spike proteins can be utilized for development of nucleic acid vaccines against infections with coronaviruses.

Figure 1: Protomer of SARS-CoV-2 Spike with RBD (receptor binding domain) in down conformation (left) and with RBD in up conformation (right)

“Up” conformation stabilization mutations allow for improved production yields of engineered Spike proteins. As engineered Spike protein is the antigenic reagent in many COVID-19 diagnostic tests, any Spike protein production efficiency will help keep up with the large-scale demand of diagnostic test manufacturing required for population-wide weekly COVID-19 testing.

The researchers also developed and optimized a yeast surface display engineering platform for type I viral fusion proteins. This yeast display system can be utilized to identify additional mutations that stabilize  the “up” conformation of Spike protein.

Applications

• Development of nucleic acid vaccines against coronavirus infections
• As an antigenic reagent in serological diagnostic tests
• Improve production yield of engineered Spike proteins
• Identify type I viral fusion protein mutations using a yeast display engineering platform

Opportunity

This technology is available for exclusive or licensing.