Immunogenic Properties of the DNA Construct Encoding the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein

M B Borgoyakova; L I Karpenko; A P Rudometov; D V Shanshin; A A Isaeva; V S Nesmeyanova; N V Volkova; S V Belenkaya; D E Murashkin; D N Shcherbakov; E A Volosnikova; E V Starostina; L A Orlova; N V Danilchenko; A V Zaikovskaya; O V Pyankov; A A Ilyichev

doi:10.1134/S0026893321050046

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. Epub 2021 Dec 17.

Authors

M B Borgoyakova¹, L I Karpenko¹, A P Rudometov¹, D V Shanshin¹, A A Isaeva^{1

2}, V S Nesmeyanova^{1

2}, N V Volkova¹, S V Belenkaya¹, D E Murashkin¹, D N Shcherbakov^{1

2}, E A Volosnikova¹, E V Starostina¹, L A Orlova¹, N V Danilchenko¹, A V Zaikovskaya¹, O V Pyankov¹, A A Ilyichev¹

Affiliations

¹ Vector State Research Center of Virology and Biotechnology, Russian Federal State Agency for Health and Consumer Rights Surveillance, 630559 Koltsovo, Novosibirsk oblast Russia.
² World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program for the Development of Genetic Technologies, Vector State Research Center of Virology and Biotechnology, Russian Federal State Agency for Health and Consumer Rights Surveillance, 630559 Koltsovo, Novosibirsk oblast Russia.

Abstract

The development of preventive vaccines became the first order task in the COVID-19 pandemic caused by SARS-CoV-2. This paper reports the construction of the pVAX-RBD plasmid containing the Receptor-Binding Domain (RBD) of the S protein and a unique signal sequence 176 which promotes target protein secretion into the extracellular space thereby increasing the efficiency of humoral immune response activation. A polyglucine-spermidine conjugate (PGS) was used to deliver pVAX-RBD into the cells. The comparative immunogenicity study of the naked pVAX-RBD and pVAX-RBD enclosed in the PGS envelope showed that the latter was more efficient in inducing an immune response in the immunized mice. In particular, RBD-specific antibody titers were shown in ELISA to be no higher than 1 : 1000 in the animals from the pVAX-RBD group and 1 : 42 000, in the pVAX-RBD-PGS group. The pVAX-RBD‒PGS construct effectively induced cellular immune response. Using ELISpot, it has been demonstrated that splenocytes obtained from the immunized animals effectively produced INF-γ in response to stimulation with the S protein-derived peptide pool. The results suggest that the polyglucine-spermidine conjugate-enveloped pVAX-RBD construct may be considered as a promising DNA vaccine against COVID-19.

Keywords: DNA vaccine; SARS-CoV-2; immune response; mouse model.

© Pleiades Publishing, Inc. 2021, ISSN 0026-8933, Molecular Biology, 2021, Vol. 55, No. 6, pp. 889–898. © Pleiades Publishing, Inc., 2021.Russian Text © The Author(s), 2021, published in Molekulyarnaya Biologiya, 2021, Vol. 55, No. 6, pp. 987–998.