Structural and computational design of a SARS-CoV-2 spike antigen with improved expression and immunogenicity

• DOI: 10.1126/sciadv.adg0330
• Publication Date: 2023-06-07T17:58:30Z
• Authors: James A. Williams; Marco Biancucci; Laura Lessen; Sai Tian; Ankita Balsaraf; Lynn Chen; Chelsy Chesterman; Giulietta Maruggi; Sarah Vandepaer; Ying Huang; Corey P. Mallett; Ann-Muriel Steff; Matthew James Bot...; Enrico Malito; Newton Wahome; Wayne D. Harshbarger
• Keywords: Antigenicity; Coronavirus

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern challenge the efficacy approved vaccines, emphasizing need for updated spike antigens. Here, we use an evolutionary-based design aimed at boosting protein expression levels S-2P and improving immunogenic outcomes in mice. Thirty-six prototype antigens were generated silico 15 produced biochemical analysis. S2D14, which contains 20 computationally designed mutations within S2 domain a rationally engineered D614G mutation SD2 domain, has ~11-fold increase yield retains RBD antigenicity. Cryo-electron microscopy structures reveal mixture populations various conformational states. Vaccination mice with adjuvanted S2D14 elicited higher cross-neutralizing antibody titers than against SARS-CoV-2 Wuhan strain four concern. may be useful scaffold or tool future approaches used broadly applicable to streamline vaccine discovery.