Major role of S-glycoprotein in providing immunogenicity and protective immunity in mRNA lipid nanoparticle vaccines based on SARS-CoV-2 structural proteins

Bykonia, E. N.; Kleymenov, D. A.; Gushchin, V. A.; Sinyavin, A. E.; Mazunina, E. P.; Kuznetsova, N.; Kozlova, S. R.; Zolotar, A. N.; Shidlovskaya, E. V.; Usachev, E. V.; Pochtovyi, A. A.; Kustova, D. D.; Ivanov, I. A.; Dmitriev, S. E.; Ivanov, R. A.; Logunov, D. Y.; Gintsburg, A. L.

doi:10.1101/2023.12.30.573713

bioRxiv · 10.1101/2023.12.30.573713

Major role of S-glycoprotein in providing immunogenicity and protective immunity in mRNA lipid nanoparticle vaccines based on SARS-CoV-2 structural proteins

Bykonia, E. N.·Kleymenov, D. A.·Gushchin, V. A.·Sinyavin, A. E.·Mazunina, E. P.·Kuznetsova, N.·Kozlova, S. R.·Zolotar, A. N.·Shidlovskaya, E. V.·Usachev, E. V.·Pochtovyi, A. A.·Kustova, D. D.·Ivanov, I. A.·Dmitriev, S. E.·Ivanov, R. A.·Logunov, D. Y.·Gintsburg, A. L.

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Abstract

Recently we have developed an mRNA lipid nanoparticle (mRNA-LNP) platform providing efficient long-term expression of an encoded gene in vivo after both intramuscular and intravenous application. Based on this platform, we have generated mRNA-LNP coding SARS-CoV-2 structural proteins M, N, S from different virus variants and studied their immunogenicity separately or in combinations in vivo. As a result, all candidate vaccine compositions coding S and N proteins induced excellent anti-RBD and N titers of binding antibodies. T cell responses mainly represented specific CD4+ T cell lymphocyte producing IL-2 and TNF-. mRNA-LNP coding M protein did not show high immunogenicity. High neutralizing activity was detected in sera of mice vaccinated with mRNA-LNP coding S protein (alone or in combinations) against closely related strains but was not detectable or significantly lower against an evolutionarily distant variant. Our data showed that the addition of mRNAs encoding S and M antigens to the mRNA-N in the vaccine composition enhanced immunogenicity of mRNA-N inducing more robust immune response to the N protein. Based on our results, we suggested that the S protein plays a key role in enhancement of immune response to the N protein in the mRNA-LNP vaccine.

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Bykonia, E. N., Kleymenov, D. A., Gushchin, V. A., Sinyavin, A. E., Mazunina, E. P., Kuznetsova, N., Kozlova, S. R., Zolotar, A. N., Shidlovskaya, E. V., Usachev, E. V., Pochtovyi, A. A., Kustova, D. D., Ivanov, I. A., Dmitriev, S. E., Ivanov, R. A., Logunov, D. Y., Gintsburg, A. L.. 2024-01-02. Major role of S-glycoprotein in providing immunogenicity and protective immunity in mRNA lipid nanoparticle vaccines based on SARS-CoV-2 structural proteins. https://doi.org/10.1101/2023.12.30.573713

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