Vaccines. Volume 12, Issue 4 (April 2024)
Affiliations
- .Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology Named after Honorary Academician N. F. Gamaleya" of the Ministry of Health of the Russian Federation, Moscow 123098, Russia.
- Department of Virology, Lomonosov Moscow State University, Moscow 119234, Russia.
- Department of Medical Genetics, Federal State Autonomous Educational Institution of Higher Education I M Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow 119991, Russia.
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow 117997, Russia.
- Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119234, Russia.
- Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119991, Russia.
- Translational Medicine Research Center, Sirius University of Science and Technology, Sochi 354340, Russia.
- Infectiology Department, I. M. Sechenov First Moscow State Medical University, Moscow 119991, Russia.
PMID: 38675761 DOI: PMC11053793 DOI: 10.3390/vaccines12040379
Abstract
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.
Keywords: SARS-CoV-2; efficacy; immunogenicity; lipid nanoparticles; mRNA vaccine.
References
- Miller J., Hachmann N.P., Collier A.-R.Y., Lasrado N., Mazurek C.R., Patio R.C., Powers O., Surve N., Theiler J., Korber B., et al. Substantial Neutralization Escape by SARS-CoV-2 Omicron Variants BQ.1.1 and XBB.1. N. Engl. J. Med. 2023;388:662–664. doi: 10.1056/NEJMc2214314.
- Hachmann N.P., Miller J., Collier A.-R.Y., Ventura J.D., Yu J., Rowe M., Bondzie E.A., Powers O., Surve N., Hall K., et al. Neutralization Escape by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4, and BA.5. N. Engl. J. Med. 2022;387:86–88. doi: 10.1056/NEJMc2206576.
- Iketani S., Liu L., Guo Y., Liu L., Chan J.F.-W., Huang Y., Wang M., Luo Y., Yu J., Chu H., et al. Antibody Evasion Properties of SARS-CoV-2 Omicron Sublineages. Nature. 2022;604:553–556. doi: 10.1038/s41586-022-04594-4.
- Interim Statement on the Composition of Current COVID-19 Vaccines. [(accessed on 29 December 2023)].
- US Food and Drug Administration Coronavirus (COVID-19) Update: FDA Authorizes Moderna, Pfizer-BioNTech Bivalent COVID-19 Vaccines for Use as a Booster Dose. United States: FDA. [(accessed on 24 October 2022)];
