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Basic Characteristics of Mutations
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Mutation Site
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S6P |
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Mutation Site Sentence
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S6P mutation in Delta and Omicron variant spike protein significantly enhances the efficacy of mRNA COVID-19 vaccines. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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S |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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Delta;Omicron |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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39830514
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Title
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S6P mutation in Delta and Omicron variant spike protein significantly enhances the efficacy of mRNA COVID-19 vaccines
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Author
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Bong YS,Brown D,Chung E,Ananthaswamy N,Chen R,Lewoczko E,Sabbers W,Patterson-Orazem AC,Dorsey Z,Zou Y,Yu X,Liang J,He J,Long S,Shen D
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Journal
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Frontiers in immunology
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Journal Info
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2025 Jan 3;15:1495561
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Abstract
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BACKGROUND: The unrelenting emergence of SARS-CoV-2 variants has significantly challenged the efficacy of existing COVID-19 vaccines. Enhancing the stability and immunogenicity of the spike protein is critical for improving vaccine performance and addressing variant-driven immune evasion. METHODS: We developed an mRNA-based vaccine, RV-1730, encoding the Delta variant spike protein with the S6P mutation to enhance stability and immunogenicity. The vaccine's immunogenicity and protective efficacy were evaluated in preclinical models, including monovalent (RV-1730) and bivalent (RV-1731) formulations targeting the Delta and BA.1 variants. Additionally, the effectiveness of RV-1730 as a heterologous booster following primary vaccination with BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna-NIAID) was assessed. RESULTS: RV-1730 elicited significantly stronger B and T cell responses and more durable neutralizing antibodies compared to S2P-based vaccines. The bivalent RV-1731 vaccine demonstrated broad neutralizing activity against emerging variants, including XBB1.5 and JN.1. Importantly, RV-1730, when used as a heterologous booster following initial immunization with BNT162b2 or mRNA-1273, significantly enhanced neutralizing antibody titers against multiple variants, including Delta and Omicron. Both RV-1730 and RV-1731 provided superior protection in preclinical models, indicating enhanced efficacy due to the S6P mutation. CONCLUSION: The incorporation of the S6P mutation into the Delta variant spike protein significantly enhances the immunogenicity and efficacy of mRNA-based COVID-19 vaccines. The strong performance of RV-1730 as a heterologous booster and the broad-spectrum activity of the bivalent RV-1731 vaccine underscore their potential as versatile and effective vaccination strategies against SARS-CoV-2 and its evolving variants.
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Sequence Data
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-
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