Cold sensitivity of the SARS-CoV-2 spike ectodomain

By R. Edwards, K. Mansouri, V. Stalls, K. Manne, Brian E Watts, R. Parks, Katarzyna Janowska, S. Gobeil, Megan Kopp, Dapeng Li and 13 more. 2021

74 citations recorded by the source corpus.

The SARS-CoV-2 spike (S) protein, a primary target for COVID-19 vaccine development, presents its receptor binding domain in two conformations, the receptor-accessible ‘up’ or receptor-inaccessible ‘down’ states. Here we report that the commonly used stabilized S ectodomain construct ‘2P’ is sensitive to cold temperatures, and this cold sensitivity is abrogated in a ‘down’ state-stabilized ectodomain. Our findings will impact structural, functional and vaccine studies that use the SARS-CoV-2 S ectodomain. The SARS-CoV-2 spike ectodomain is destabilized by cold temperature storage, an effect that can be reversed by incubation at 37 °C or by stabilizing its conformation in the ‘down’ state.

Subfields: Animal Science and Zoology, Epidemiology, Infectious Diseases

Citations in the corpus

• Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, neutral): “…components and the robust stability of the antigen-bearing RBD nanoparticles suggests that these will likely be more amenable to large-scale manufacturing than the SARS-CoV-2 S-2P trimer, which expresses poorly and is unstable (Edwards et al., 2020; Hsieh et al., 2020; McCallum et al., 2020).”