SARS-CoV-2 Spike Protein Stabilized in the Closed State Induces Potent Neutralizing Responses
George Carnell, Katarzyna A. Ciazynska, David A. Wells, Xiaoli Xiong, Ernest T. Aguinam, Stephen H. McLaughlin, Donna L. Mallery, Soraya Ebrahimi, Lourdes Ceron‐Gutierrez, Benedikt Asbach, Sebastian Einhauser, Ralf Wagner, Leo C. James, Rainer Döffinger, Jonathan L. Heeney, John A. G. Briggs
Abstract
Vaccines in use against SARS-CoV-2 induce immune responses against the spike protein. There is intense interest in whether the antibody response induced by vaccines will be robust against new variants, as well as in next-generation vaccines for use in previously infected or immunized individuals. We assessed the use as an immunogen of a spike protein engineered to be conformationally stabilized in the closed state where the receptor binding site is occluded. Despite occlusion of the receptor binding site, the spike induces potently neutralizing sera against multiple SARS-CoV-2 variants. Antibodies are raised against a different pattern of epitopes to those induced by other spike constructs, preferring conformational epitopes present in the closed conformation. Closed spikes, or mRNA vaccines based on their sequence, can be a valuable component of next-generation vaccines.