tetano
Editor, Senior Moderator
Sci Adv
. 2023 Jun 9;9(23):eadg0330.
doi: 10.1126/sciadv.adg0330. Epub 2023 Jun 7. Structural and computational design of a SARS-CoV-2 spike antigen with improved expression and immunogenicity
James A Williams[SUP] 1 [/SUP], Marco Biancucci[SUP] 1 [/SUP], Laura Lessen[SUP] 1 [/SUP], Sai Tian[SUP] 1 [/SUP], Ankita Balsaraf[SUP] 1 [/SUP], Lynn Chen[SUP] 1 [/SUP], Chelsy Chesterman[SUP] 1 [/SUP], Giulietta Maruggi[SUP] 1 [/SUP], Sarah Vandepaer[SUP] 1 [/SUP], Ying Huang[SUP] 1 [/SUP], Corey P Mallett[SUP] 1 [/SUP], Ann-Muriel Steff[SUP] 1 [/SUP], Matthew James Bottomley[SUP] 1 [/SUP], Enrico Malito[SUP] 1 [/SUP], Newton Wahome[SUP] 1 [/SUP], Wayne D Harshbarger[SUP] 1 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern challenge the efficacy of approved vaccines, emphasizing the need for updated spike antigens. Here, we use an evolutionary-based design aimed at boosting protein expression levels of S-2P and improving immunogenic outcomes in mice. Thirty-six prototype antigens were generated in silico and 15 were produced for biochemical analysis. S2D14, which contains 20 computationally designed mutations within the S2 domain and a rationally engineered D614G mutation in the SD2 domain, has an ~11-fold increase in protein yield and retains RBD antigenicity. Cryo-electron microscopy structures reveal a mixture of populations in various RBD conformational states. Vaccination of mice with adjuvanted S2D14 elicited higher cross-neutralizing antibody titers than adjuvanted S-2P against the SARS-CoV-2 Wuhan strain and four variants of concern. S2D14 may be a useful scaffold or tool for the design of future coronavirus vaccines, and the approaches used for the design of S2D14 may be broadly applicable to streamline vaccine discovery.
. 2023 Jun 9;9(23):eadg0330.
doi: 10.1126/sciadv.adg0330. Epub 2023 Jun 7. Structural and computational design of a SARS-CoV-2 spike antigen with improved expression and immunogenicity
James A Williams[SUP] 1 [/SUP], Marco Biancucci[SUP] 1 [/SUP], Laura Lessen[SUP] 1 [/SUP], Sai Tian[SUP] 1 [/SUP], Ankita Balsaraf[SUP] 1 [/SUP], Lynn Chen[SUP] 1 [/SUP], Chelsy Chesterman[SUP] 1 [/SUP], Giulietta Maruggi[SUP] 1 [/SUP], Sarah Vandepaer[SUP] 1 [/SUP], Ying Huang[SUP] 1 [/SUP], Corey P Mallett[SUP] 1 [/SUP], Ann-Muriel Steff[SUP] 1 [/SUP], Matthew James Bottomley[SUP] 1 [/SUP], Enrico Malito[SUP] 1 [/SUP], Newton Wahome[SUP] 1 [/SUP], Wayne D Harshbarger[SUP] 1 [/SUP]
Affiliations
- PMID: 37285422
- DOI: 10.1126/sciadv.adg0330
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern challenge the efficacy of approved vaccines, emphasizing the need for updated spike antigens. Here, we use an evolutionary-based design aimed at boosting protein expression levels of S-2P and improving immunogenic outcomes in mice. Thirty-six prototype antigens were generated in silico and 15 were produced for biochemical analysis. S2D14, which contains 20 computationally designed mutations within the S2 domain and a rationally engineered D614G mutation in the SD2 domain, has an ~11-fold increase in protein yield and retains RBD antigenicity. Cryo-electron microscopy structures reveal a mixture of populations in various RBD conformational states. Vaccination of mice with adjuvanted S2D14 elicited higher cross-neutralizing antibody titers than adjuvanted S-2P against the SARS-CoV-2 Wuhan strain and four variants of concern. S2D14 may be a useful scaffold or tool for the design of future coronavirus vaccines, and the approaches used for the design of S2D14 may be broadly applicable to streamline vaccine discovery.