tetano
Editor, Senior Moderator
Front Immunol
. 2025 Jan 3:15:1495561.
doi: 10.3389/fimmu.2024.1495561. eCollection 2024. S6P mutation in Delta and Omicron variant spike protein significantly enhances the efficacy of mRNA COVID-19 vaccines
Yong-Sik Bong[SUP] #[/SUP][SUP] 1 [/SUP], David Brown[SUP] #[/SUP][SUP] 1 [/SUP], Ezra Chung[SUP] #[/SUP][SUP] 1 [/SUP], Neeti Ananthaswamy[SUP] 1 [/SUP], Renxiang Chen[SUP] 1 2 [/SUP], Evan Lewoczko[SUP] 1 [/SUP], William Sabbers[SUP] 1 [/SUP], Athéna C Patterson-Orazem[SUP] 1 [/SUP], Zachary Dorsey[SUP] 1 [/SUP], Yiqing Zou[SUP] 2 [/SUP], Xue Yu[SUP] 2 [/SUP], Jiening Liang[SUP] 2 [/SUP], Jiaxi He[SUP] 2 [/SUP], Steven Long[SUP] 1 [/SUP], Dong Shen[SUP] 1 [/SUP]
Affiliations
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.
Keywords: Delta and Omicron variant; RV-1730 and RV-1731 vaccines; SARS-CoV-2 spike protein; immunogenicity; lipid nanoparticles (LNPs); mRNA vaccines; neutralizing antibodies
. 2025 Jan 3:15:1495561.
doi: 10.3389/fimmu.2024.1495561. eCollection 2024. S6P mutation in Delta and Omicron variant spike protein significantly enhances the efficacy of mRNA COVID-19 vaccines
Yong-Sik Bong[SUP] #[/SUP][SUP] 1 [/SUP], David Brown[SUP] #[/SUP][SUP] 1 [/SUP], Ezra Chung[SUP] #[/SUP][SUP] 1 [/SUP], Neeti Ananthaswamy[SUP] 1 [/SUP], Renxiang Chen[SUP] 1 2 [/SUP], Evan Lewoczko[SUP] 1 [/SUP], William Sabbers[SUP] 1 [/SUP], Athéna C Patterson-Orazem[SUP] 1 [/SUP], Zachary Dorsey[SUP] 1 [/SUP], Yiqing Zou[SUP] 2 [/SUP], Xue Yu[SUP] 2 [/SUP], Jiening Liang[SUP] 2 [/SUP], Jiaxi He[SUP] 2 [/SUP], Steven Long[SUP] 1 [/SUP], Dong Shen[SUP] 1 [/SUP]
Affiliations
- PMID: 39830514
- PMCID: PMC11739128
- DOI: 10.3389/fimmu.2024.1495561
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.
Keywords: Delta and Omicron variant; RV-1730 and RV-1731 vaccines; SARS-CoV-2 spike protein; immunogenicity; lipid nanoparticles (LNPs); mRNA vaccines; neutralizing antibodies