Abstract
The spike protein of SARS-CoV-2 is essential for virus entry into human cells and is also the main antigenic determinant of the virus, being therefor essential to induce and detect antibodies. As a consequence, the global demand for spike proteins has rapidly increased and could exceed hundreds of grams to kilograms annually. Coronavirus spikes are large, heavily glycosylated, homotrimeric complexes, with inherent instability. Their poor manufacturability now threatens the availability of these proteins for large scale manufacture of vaccines and diagnostic tests. Here, we outline a scalable, GMP-ready, chemically defined process for production of a stabilized form of the trimeric spike protein. The process is chemically defined and based on a clonal, suspension-CHO cell line and purification of the protein via a two-step, scalable downstream process. The trimeric conformation was confirmed using Cryo-EM and HPLC analysis. Binding to SARS-CoV-2 host cells was shown using a virus-inhibition assay. The diagnostic sensitivity and specificity for detection of serum SARS-CoV-2 specific IgG1 was investigated and found to exceed that of spike fragments (S1 and RBD).