Post-genomic platform for development of oligonucleotide vaccines against RNA viruses: diamond cuts diamond

Abstract

The coronavirus pandemic has starkly demonstrated the need to create highly effective vaccines against various viral diseases. The emerging new platforms for vaccine creation (adenovirus vectors and mRNA vaccines) have shown their worth in the fight against the prevention of coronavirus infection. However, adenovirus vectors and mRNA vaccines have a serious disadvantage: as a rule, only the S protein of the coronavirus is presented as an antigen. This tactic for preventing infection allows the ever-mutating virus to escape quickly from the immunity protection provided by such vaccines. Today, viral genomic databases are well-developed, which makes it possible to create new vaccines on a fundamentally new post-genomic platform. In addition, the technology for the synthesis of nucleic acids is currently experiencing an upsurge in demand in various fields of molecular biology. The accumulated experience suggests that the unique genomic sequences of viruses can act as antigens that trigger powerful humoral and cellular immunity. To achieve this effect, the following conditions must be created: the structure of the nucleic acid must be single-stranded, have a permanent 3D nanostructure, and have a unique sequence absent in the vaccinated organism. Oligonucleotide vaccines are able to resist the rapidly changing genomic sequences of RNA viruses by using conserved regions of their genomes to generate a long-term immune response, acting according to the adage that a diamond cuts a diamond. In addition, oligonucleotide vaccines will not contribute to antibody-dependent enhanced infection, since the nucleic acid of the coronavirus is inside the viral particle. It is obvious that new epidemics and pandemics caused by RNA viruses will continue to arise periodically in the human population. The creation of new, safe, and effective platforms for the production of vaccines that can flexibly change and adapt to new subtypes of viruses is very urgent and at this moment should be considered as a strategically necessary task.

Keywords: Immunity; La-S-so; Oligonucleotide vaccine; Pandemic; Post-genomic platform; RNA viruses; SARS-CoV-2.

Fig. 1

Presumptive scheme of action of oligonucleotide vaccines: pathways supporting B cell and T cell activation are discussed

Fig. 2

Variants of oligonucleotide vaccines A semi-natural (has inserts (A*) of oligonucleotides that do not belong to the RNA virus [54]), B natural (consists of the full RNA virus genome fragment). The constructs are performed by RNAfold WebServer; https://rna.tbi.univie.ac.at)