Cellular immune response to DNA vaccine encoding receptor-binding domain of SARS-CoV-2 S protein: dependence on the packing mode
- Authors: Borgoyakova M.B.1, Karpenko L.I.1, Starostina E.V.1, Volosnikova E.A.1, Zadorozhny A.M.1, Orlova L.A.1, Ilyichev A.A.1
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Affiliations:
- State Research Centre of Virology and Biotechnology “Vector”
- Issue: Vol 25, No 2 (2022)
- Pages: 131-138
- Section: SHORT COMMUNICATIONS
- URL: https://journals.rcsi.science/1028-7221/article/view/120160
- DOI: https://doi.org/10.46235/1028-7221-1114-CIR
- ID: 120160
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Abstract
Massive vaccination against SARS-CoV-2 appears to be one of the most important steps towards solving the problem of the COVID-19 pandemic, which threatened the lives of millions of people over two and a half years. To create anti-COVID-19 vaccines, both traditional approaches (inactivated vaccines), and innovative efforts were used, including the nucleic acid-based vaccines (mRNA, DNA vaccines) which appeared on the market. We constructed a plasmid (DNA vaccine) encoding the gene for the receptor-binding domain (RBD) of spike protein (S) of the SARS-CoV-2 virus. This DNA vaccine was named pVAXrbd. The polycationic carrier polyglucin-spermidine (PGS) and its recombinant RBD protein conjugate (PGS-RBD) were used to package pVAXrbd. By adding the negatively charged DNA pVAXrbd plasmid to polycationic PGS or PGS-RBD molecules, the complexes of polymers with plasmid DNA were formed by self-assembly, due to their non-covalent interaction. The aim of this work was to study cellular response induced by the DNA vaccine at various packaging options, as well as to analyze influence of the vaccine packaging upon development of the immune response. BALB/c mice were injected with DNA vaccine in three versions: “naked” pVAXrbd; plasmid pVAXrbd in PGS envelope; pVAXrbd in PGS-RBD wrapper. In control group, the animals were injected with the recombinant RBD protein. Cellular response was assessed by the IFNγ production using two methods, i.e., ELISpot and ICS using flow cytometry. It was shown that the DNA vaccine pVAXrbd, both per se, or as part of complexes, showed the ability to induce cellular immune response. The most effective cellular immune response was found in the group of animals immunized with pVAXrbd-PGS complex. Using ELISpot detection technique for this group, the largest number of cells responding by IFNγ release was registered upon stimulation with specific peptides; usage of ICS and flow cytometry for evaluation in this group showed higher percentage of IFNγ-producing CD4+ and CD8+T cells. This observed effect could be explained by DNA protection from nuclease action by the polyglucin-spermidine envelope. The pVAXrbd-PGS complexes may be also more efficiently recognized by antigen-presenting cells than naked plasmid DNA. The presented results show that the polyglucin-spermidine envelope provides an increase in immunogenicity of the DNA vaccine pVAXrbd, in terms of virus-specific T cell response.
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##article.viewOnOriginalSite##About the authors
Mariya B. Borgoyakova
State Research Centre of Virology and Biotechnology “Vector”
Author for correspondence.
Email: borgoyakova_mb@vector.nsc.ru
ORCID iD: 0000-0002-0768-1561
SPIN-code: 8588-7391
Scopus Author ID: 57221732585
Junior Research Associate, Center of Genomic Studies in Biological Safety
Russian Federation, Koltsovo, Novosibirsk Region, 630559Larisa I. Karpenko
State Research Centre of Virology and Biotechnology “Vector”
Email: karpenko@vector.nsc.ru
PhD, MD (Biology), Associate Professor, Leading Research Associate, Center of Genomic Studies in Biological Safety
Russian Federation, Koltsovo, Novosibirsk Region, 630559Ekaterina V. Starostina
State Research Centre of Virology and Biotechnology “Vector”
Email: starostina_ev@vector.nsc.ru
PhD (Biology), Research Associate, Center of Genomic Studies in Biological Safety
Russian Federation, Koltsovo, Novosibirsk Region, 630559Ekaterina A. Volosnikova
State Research Centre of Virology and Biotechnology “Vector”
Email: volosnikova_ea@vector.nsc.ru
PhD (Biology), Leading Research Associate, Center of Genomic Studies in Biological Safety
Russian Federation, Koltsovo, Novosibirsk Region, 630559Alexey M. Zadorozhny
State Research Centre of Virology and Biotechnology “Vector”
Email: zadorozhnyy_am@vector.nsc.ru
Research Trainee, Center of Genomic Studies in Biological Safety
Russian Federation, Koltsovo, Novosibirsk Region, 630559Lyubov A. Orlova
State Research Centre of Virology and Biotechnology “Vector”
Email: orlova_la@vector.nsc.ru
Postgraduate Student, Research Trainee, Center of Genomic Studies in Biological Safety
Russian Federation, Koltsovo, Novosibirsk Region, 630559Alexander A. Ilyichev
State Research Centre of Virology and Biotechnology “Vector”
Email: ilyichev@vector.nsc.ru
PhD, MD (Biology), Professor, Head, Department of Bioengineering, Center of Genomic Studies in Biological Safety
Russian Federation, Koltsovo, Novosibirsk Region, 630559References
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