Immunogenicity of mRNA encoding RBD SARS-CoV-2 in complex with a polycationic carrier

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

BACKGROUND: RBD, receptor-binding domain, a key region of the SARS-CoV-2 surface glycoprotein for virus binding to host cell receptors and one of the targets of virus-neutralizing antibodies. That is why RBD is a promising immunogen for the development of vaccines that can provide protection against COVID-19. Vaccine mRNA is one of the new and rapidly developing vaccine platforms, and the delivery system is a very important component of it.

AIM: The aim of this work was to present the results of a study of the antigenic properties of mRNA encoding the receptor-binding domain of SARS-CoV-2 when administered in combination with a polycationic carrier.

MATERIALS AND METHODS: Dynamic and electrophoretic light scattering were used to characterize mRNA complexes with a polyglucin-spermidine conjugate. To assess the immunogenicity of mRNA were immunized BALB/c mice. The specific activity of the sera was assessed using enzyme immunoassay.

RESULTS: As a result, the sizes and surface charge of the RBD-encoding mRNA complexes with the polyglucin-spermidine conjugate were determined. It has been shown that wrapping mRNA in a polyglucin-spermidine conjugate shell leads to an increase in the induction of RBD-specific antibodies in BALB/c mice compared to naked mRNA.

CONCLUSIONS: An mRNA encoding the receptor-binding domain of SARS-CoV-2 has been obtained. It has been shown that the packaging of mRNA into the polyglucin-spermidine conjugate shell leads to an increase in immunogenic properties.

Full Text

Restricted Access

About the authors

Andrey P. Rudometov

State Research Center of Virology and Biotechnology “Vector”, Federal Service for Surveillance on Consumer Rights Protection and Human Well-being

Author for correspondence.
Email: andrei692@mail.ru
ORCID iD: 0000-0003-2808-4309
SPIN-code: 7245-2291

Cand. Sci. (Biol.), Senior Research Associate

Russian Federation, Koltsovo, Novosibirsk Region

Sergey V. Sharabrin

State Research Center of Virology and Biotechnology “Vector”, Federal Service for Surveillance on Consumer Rights Protection and Human Well-being

Email: sharabrin_sv@vector.nsc.ru
ORCID iD: 0000-0003-0664-3587
Scopus Author ID: 57221380569

Junior Research Associate

Russian Federation, Koltsovo, Novosibirsk Region

Maria B. Borgoyakova

State Research Center of Virology and Biotechnology “Vector”, Federal Service for Surveillance on Consumer Rights Protection and Human Well-being

Email: borgoyakova_mb@vector.nsc.ru
ORCID iD: 0000-0002-0768-1561
Scopus Author ID: 57221732585

Junior Research Associate

Russian Federation, Koltsovo, Novosibirsk Region

Ekaterina A. Volosnikova

State Research Center of Virology and Biotechnology “Vector”, Federal Service for Surveillance on Consumer Rights Protection and Human Well-being

Email: volosnikova_ea@vector.nsc.ru
ORCID iD: 0000-0001-5028-5647

Cand. Sci. (Biol.), Leading Research Associate

Russian Federation, Koltsovo, Novosibirsk Region

Nadezhda B. Rudometova

State Research Center of Virology and Biotechnology “Vector”, Federal Service for Surveillance on Consumer Rights Protection and Human Well-being

Email: nadenkaand100@mail.ru
ORCID iD: 0000-0002-1684-9071
SPIN-code: 5283-6608

Cand. Sci. (Biol.), Research Associate

Russian Federation, Koltsovo, Novosibirsk Region

Lyubov A. Orlova

State Research Center of Virology and Biotechnology “Vector”, Federal Service for Surveillance on Consumer Rights Protection and Human Well-being

Email: orlova_la@vector.nsc.ru
ORCID iD: 0000-0001-7214-1855

Research Assistant

Russian Federation, Koltsovo, Novosibirsk Region

Alexander A. Ilyichev

State Research Center of Virology and Biotechnology “Vector”, Federal Service for Surveillance on Consumer Rights Protection and Human Well-being

Email: ilyichev@vector.nsc.ru
ORCID iD: 0000-0001-5356-0843
Scopus Author ID: 7006402361
ResearcherId: B-1327-2012

Dr. Sci. (Biol.), Professor, Head of the Department of Bioengineering

Russian Federation, Koltsovo, Novosibirsk Region

Larisa I. Karpenko

State Research Center of Virology and Biotechnology “Vector”, Federal Service for Surveillance on Consumer Rights Protection and Human Well-being

Email: karpenko@vector.nsc.ru
ORCID iD: 0000-0003-4365-8809
SPIN-code: 2026-5992
Scopus Author ID: 7005000410

Dr. Sci. (Biol.), Assistant Professor, Leading Research Associate

Russian Federation, Koltsovo, Novosibirsk Region

References

  1. Kleanthous H, Silverman JM, Makar KW, et al. Scientific rationale for developing potent RBD-based vaccines targeting COVID-19. NPJ Vaccines. 2021;6(1):128. doi: 10.1038/s41541-021-00393-6
  2. Borgoyakova MB, Karpenko LI, Rudometov AP, et al. Self-assembled particles combining SARS-CoV-2 RBD Protein and RBD DNA vaccine induce synergistic enhancement of the humoral response in mice. Int J Mol Sci. 2022;23(4):2188. doi: 10.3390/ijms23042188
  3. Merkuleva IA, Shcherbakov DN, Borgoyakova MB, et al. comparative immunogenicity of the recombinant receptor-binding domain of protein S SARS-CoV-2 obtained in prokaryotic and mammalian expression systems. Vaccines (Basel). 2022;10(1):96. doi: 10.3390/vaccines10010096
  4. Borgoyakova MB, Karpenko LI, Rudometov AP, et al. Immunogenic properties of the DNA construct encoding the receptor-binding domain of the SARS-CoV-2 spike protein. Mol Biol. 2021;55(6):889–898. doi: 10.1134/S0026893321050046
  5. Szabó GT, Mahiny AJ, Vlatkovic I. COVID-19 mRNA vaccines: platforms and current developments. Mol Ther. 2022;30(5):1850–1868. doi: 10.1016/j.ymthe.2022.02.016
  6. Salleh MZ, Norazmi MN, Deris ZZ. Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2. Peer J. 2022;10:e13083. doi: 10.7717/peerj.13083
  7. Karpenko LI, Rudometov AP, Sharabrin SV, et al. Delivery of mRNA vaccine against SARS-CoV-2 using a polyglucin: Spermidine conjugate. Vaccines (Basel). 2021;9(2):76. doi: 10.3390/vaccines9020076
  8. Starostina EV, Sharabrin SV, Antropov DN, et al. Construction and immunogenicity of modified mRNA-vaccine variants encoding influenza virus antigens. Vaccines (Basel). 2021;9(5):452. doi: 10.3390/vaccines9050452
  9. Karpenko LI, Apartsin EK, Dudko SG, et al. Cationic polymers for the delivery of the Ebola DNA vaccine encoding artificial T-сell immunogen. Vaccines (Basel). 2020;8(4):718. doi: 10.3390/vaccines8040718
  10. Sahin U, Muik A, Derhovanessian E, et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH 1T cell responses. Nature. 2020;586(7830):594–599. doi: 10.1038/s41586-020-2814-7

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. Electrophoregram of separation of RNA and mRNA GFP and RBD (a): 1 — RNA-GFP before polyadenylation; 2 — mRNA-GFP after polyadenylation; 3 — RNA-RBD before polyadenylation; 4 — mRNA-RBD after polyadenylation. Micrograph of HEK293 transfected with mRNA-GFP, 10x magnification (b)

Download (122KB)
3. Fig. 2. Titers of specific IgG antibodies to RBD SARS-CoV-2. Data are presented as mean ± standard deviation. Statistical significance was calculated using two-way analysis of variance with multiple comparison tests. n. s. — not statistically significant; * p < 0.01, ** p < 0.001

Download (97KB)

Copyright (c) 2022 Eco-Vector



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 74760 от 29.12.2018 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies