«DELTA-VAC» SUBUNIT VACCINE INDUCES STRONG HUMORAL IMMUNE RESPONSE AGAINST SARS-COV-2

Abstract

Introduction: The COVID-19 pandemic has focused the attention of researchers around the world on the fight against this infection. A critical approach to combating COVID-19 has been the development of preventive vaccines based on a range of platforms, including DNA and RNA vaccines, vector and subunit vaccines. Subunit vaccines have become one of these platforms, primarily due to their unsurpassed safety profile. However, the safety of these vaccines is often associated with low effectiveness, so it is often necessary to use adjuvants, as well as use more complex immunization regimens. At the same time, an important advantage of subunit vaccines is scalability and relative ease of production, since there is no need to work with live virus or viral vectors during the production process. Our object of the work was to develop a candidate vaccine based on the recombinant receptor-binding domain (RBD) of the SARS-CoV-2 spike S-protein of the Delta variant (B.1.617.2). Materials and Methods: The study used immunological methods and methods of genetic engineering and biotechnology. Results: In the course of work based on the mammalian cells CHO-K1 developed producer of recombinant RBD. To obtain a protein that meets the requirements of injectable drugs, a chromatographic purification scheme was developed, including affinity and ion exchange chromatography. A variant of the subunit vaccine «Delta-Vac» based on the obtained recombinant protein was proposed. Assessment of the immunogenicity of the Delta-Vac vaccine was carried out on the model of laboratory mice BALB/c. Animals were immunized twice with a dose of 50 μg of RBD in combination with Al(OH)₃ at a two-week interval. The ability of the candidate vaccine to induce the production of specific IgG and neutralizing antibodies in BALB/c mice was demonstrated. The specific antibody titers of immunized animals ranged from 1/10⁵ to 1/10⁶. At the same time, blood serums had neutralizing activity against SARS-CoV-2 (variant B.1.617.2 (Delta)) with a titer of up to 1/2000. Conclusion: The vaccine "Delta-Vak» developed is highly immunogenic and induces the production of neutralizing antibodies against homologous Delta variant and heterologous Wuhan and Omicron SARS-CoV-2 variants. Thus, «Delta-Vac» can act as a vaccine candidate and serve as a prototype for the development of subunit vaccines against COVID-19.

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