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Title | Structural and computational design of a SARS-CoV-2 spike antigen with improved expression and immunogenicity. |
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Journal, issue, pages | Sci Adv, Vol. 9, Issue 23, Page eadg0330, Year 2023 |
Publish date | Jun 9, 2023 |
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 Bottomley / Enrico Malito / Newton Wahome / Wayne D Harshbarger / |
PubMed Abstract | 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 ...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. |
External links | Sci Adv / PubMed:37285422 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.8 - 3.3 Å |
Structure data | EMDB-28531, PDB-8epn: EMDB-28532, PDB-8epp: EMDB-28533, PDB-8epq: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN / Glycoprotein / trimer |