Self-Assembled Particles Combining SARS-CoV-2 RBD Protein and RBD DNA Vaccine Induce Synergistic Enhancement of the Humoral Response in Mice.

M B Borgoyakova ,Alexander V Taranin,Alexander A Ilyichev,Oleg V Pyankov,Larisa I Karpenko,Daniil V Shanshin ,А А Исаева ,А V Zaykovskaya ,Н В Волкова ,Valentina S Nesmeyanova ,Е Д Даниленко ,Л А Орлова ,Д Н Щербаков ,Alexey M Zadorozhny ,А П Рудометов ,Б Н Зайцев ,Sergei I Bazhan ,Ekaterina A Volosnikova ,Iuliia A Merkuleva ,Ekaterina V Starostina ,Konstantin Baranov

doi:10.3390/ijms23042188

Abstract

Despite the fact that a range of vaccines against COVID-19 have already been created and are used for mass vaccination, the development of effective, safe, technological, and affordable vaccines continues. We have designed a vaccine that combines the recombinant protein and DNA vaccine approaches in a self-assembled particle. The receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 was conjugated to polyglucin:spermidine and mixed with DNA vaccine (pVAXrbd), which led to the formation of particles of combined coronavirus vaccine (CCV-RBD) that contain the DNA vaccine inside and RBD protein on the surface. CCV-RBD particles were characterized with gel filtration, electron microscopy, and biolayer interferometry. To investigate the immunogenicity of the combined vaccine and its components, mice were immunized with the DNA vaccine pVAXrbd or RBD protein as well as CCV-RBD particles. The highest antigen-specific IgG and neutralizing activity were induced by CCV-RBD, and the level of antibodies induced by DNA or RBD alone was significantly lower. The cellular immune response was detected only in the case of DNA or CCV-RBD vaccination. These results demonstrate that a combination of DNA vaccine and RBD protein in one construct synergistically increases the humoral response to RBD protein in mice.

Highlights

IntroductionThe ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), requires the development of new effective vaccines [1]
The lysate and culture medium of HEK293T transfected with plasmid pVAX did not show any other proteins reactive with the mouse anti-SARS-CoV-2 antibody (Figure 1(A2), lanes 2 and 4)
There is work in which it is predicted that the generation of prophylactic COVID-19 vaccines will be protein vaccines [25]

Summary

Introduction

The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), requires the development of new effective vaccines [1]. Some of the first to be licensed were messenger RNA (mRNA) vaccines, vector vaccines, and inactivated vaccines [2–6]. Vaccines based on other approaches are emerging, including. The COVID-19 DNA vaccine, developed by Zydus Cadila (India), is the world’s first

Methods

Results

Conclusion