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

Авторы: Bykonia Evgeniia N., Kleymenov Denis A., Gushchin Vladimir A., Siniavin Andrei E., Mazunina Elena P., Kozlova Sofia R., Zolotar Anastasia N., Usachev Evgeny V., Kuznetsova Nadezhda A., Shidlovskaya Elena V., Pochtovyi Andrei A., Kustova Daria D., Ivanov Igor A., Dmitriev Sergey E., Ivanov Roman A., Logunov Denis Y., Gintsburg Alexander L.
Журнал: VACCINES
Том: 12
Номер: 4
Год издания: 2024
Первая страница: 379
Последняя страница: 379
DOI: 10.3390/vaccines12040379
Аннотация: SARS-CoV-2 variants have evolved over time in recent years, demonstrating immune evasion of vaccine-induced neutralizing antibodies directed against the original S protein. Updated S-targeted vaccines provide a high level of protection against circulating variants of SARS-CoV-2, but this protection declines over time due to ongoing virus evolution. To achieve a broader protection, novel vaccine candidates involving additional antigens with low mutation rates are currently needed. Based on our recently studied mRNA lipid nanoparticle (mRNA-LNP) platform, we have generated mRNA-LNP encoding SARS-CoV-2 structural proteins M, N, S from different virus variants and studied their immunogenicity separately or in combination in vivo. As a result, all mRNA-LNP vaccine compositions encoding the S and N proteins induced excellent titers of RBD- and N-specific binding antibodies. The T cell responses were mainly specific CD4+ T cell lymphocytes producing IL-2 and TNF-alpha. mRNA-LNP encoding the M protein did not show a high immunogenicity. High neutralizing activity was detected in the sera of mice vaccinated with mRNA-LNP encoding S protein (alone or in combinations) against closely related strains, but was undetectable or significantly lower against an evolutionarily distant variant. Our data showed that the addition of mRNAs encoding S and M antigens to mRNA-N in the vaccine composition enhanced the immunogenicity of mRNA-N and induced a more robust immune response to the N protein. Based on our results, we suggested that the S protein plays a key role in enhancing the immune response to the N protein when they are both encoded in the mRNA-LNP vaccine.
Добавил в систему: Почтовый Андрей Андреевич

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Major Role of S-Glycoprotein in Providing Immunogenicity and Protective Immunity in mRNA Lipid Nanoparticle Vaccines Based on SARS-CoV-2 Structural Proteinsстатья

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