1. RBD design increases the functional antibody titers elicited by SARS-CoV-2 spike vaccination.
- Author
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Dickey TH, Salinas ND, Patel P, Orr-Gonzalez S, Ouahes T, McAleese H, Richardson BL, Singleton M, Murphy M, Eaton B, Kwan JL, Holbrook MR, Lambert LE, and Tolia NH
- Subjects
- Animals, Mice, Humans, Vaccination, Female, Protein Domains immunology, Spike Glycoprotein, Coronavirus immunology, COVID-19 Vaccines immunology, Antibodies, Neutralizing immunology, Antibodies, Neutralizing blood, Antibodies, Viral immunology, Antibodies, Viral blood, SARS-CoV-2 immunology, COVID-19 immunology, COVID-19 prevention & control
- Abstract
Most COVID-19 vaccines contain the SARS-CoV-2 spike protein as an antigen, but they lose efficacy as neutralizing antibody titers wane and escape variants emerge. Modifying the spike antigen to increase neutralizing antibody titers would help counteract this decrease in titer. We previously used a structure-based computational design method to identify nine amino acid changes in the receptor-binding domain (RBD) of spike that stabilize the RBD and increase the neutralizing antibody titers elicited by vaccination. Here, we introduce those enhancing amino acid changes into a full-length spike (FL-S-2P) ectodomain representative of most approved vaccine antigens. These amino acid changes can be incorporated into the FL-S-2P protein without negatively effecting expression or stability. Furthermore, the amino acid changes improved functional antibody titers in both mice and monkeys following vaccination. These amino acid changes could increase the duration of protection conferred by most COVID-19 vaccines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)
- Published
- 2024
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