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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1495561
This article is part of the Research Topic SARS-CoV-2 Vaccines Beyond the Pandemic Era View all 13 articles

S6P Mutation in Delta and Omicron Variant Spike Protein Significantly Enhances the Efficacy of mRNA COVID-19 Vaccines

Provisionally accepted
Yong-Sik Bong Yong-Sik Bong 1*David Brown David Brown 1*Ezra Chung Ezra Chung 1*Neeti Ananthaswamy Neeti Ananthaswamy 1*Renxiang Chen Renxiang Chen 1*Evan Lewoczko Evan Lewoczko 1William Sabbers William Sabbers 1*Athéna C. Patterson-Orazem Athéna C. Patterson-Orazem 1Zachary Dorsey Zachary Dorsey 1Yiqing Zou Yiqing Zou 2*Xue Yu Xue Yu 2*Jiening Liang Jiening Liang 2*Jiaxi He Jiaxi He 2*Steven Long Steven Long 1*Dong Shen Dong Shen 1*
  • 1 RNAimmune, Inc., Gaithersburg, United States
  • 2 Guangzhou RNAimmune, Ltd., Guangzhou, China

The final, formatted version of the article will be published soon.

    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.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.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: Lipid nanoparticles (LNP), mRNA vaccines, SARS-CoV-2 spike protein, Immunogenicity, neutralizing antibodies, Delta and Omicron variant, RV-1730 and RV-1731 vaccines

    Received: 12 Sep 2024; Accepted: 09 Dec 2024.

    Copyright: © 2024 Bong, Brown, Chung, Ananthaswamy, Chen, Lewoczko, Sabbers, Patterson-Orazem, Dorsey, Zou, Yu, Liang, He, Long and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yong-Sik Bong, RNAimmune, Inc., Gaithersburg, United States
    David Brown, RNAimmune, Inc., Gaithersburg, United States
    Ezra Chung, RNAimmune, Inc., Gaithersburg, United States
    Neeti Ananthaswamy, RNAimmune, Inc., Gaithersburg, United States
    Renxiang Chen, RNAimmune, Inc., Gaithersburg, United States
    William Sabbers, RNAimmune, Inc., Gaithersburg, United States
    Yiqing Zou, Guangzhou RNAimmune, Ltd., Guangzhou, China
    Xue Yu, Guangzhou RNAimmune, Ltd., Guangzhou, China
    Jiening Liang, Guangzhou RNAimmune, Ltd., Guangzhou, China
    Jiaxi He, Guangzhou RNAimmune, Ltd., Guangzhou, China
    Steven Long, RNAimmune, Inc., Gaithersburg, United States
    Dong Shen, RNAimmune, Inc., Gaithersburg, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.