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.

DNA Oligonucleotides as Antivirals and Vaccine Constituents against SARS Coronaviruses: A Prospective Tool for Immune System Tuning

“…Scientists have collected sporadic but convincing data over the past decades on the possibility of using nucleic acids as an active immunogen [ 66 , 67 , 68 , 69 , 70 , 71 ].…”

Adjuvant Oligonucleotide Vaccine Increases Survival and Improves Lung Tissue Condition of B6.Cg-Tg (K18-ACE2)2 Transgenic Mice

“…Thus, from the point of view of improving the safety and duration of vaccines, the search for new platforms is relevant. Of interest is the post-genomic platform for creating vaccines [15], which is based on the use of nucleotide sequences of RNA viruses not just as adjuvants (based typically on phosphorothioate oligonucleotides containing CpG islands) but also as antigens [14][15][16]. The avalanche accumulation of SARS-CoV-2 genomic sequences contributes to this direction of the search.…”

New Advances and Perspectives of Influenza Prevention: Current State of the Art

“…Two obstacles stand in the way of the development of oligonucleotide vaccines: the lack of knowledge concerning antibodies capable of penetrating cells and attacking the unique nucleic acid sequences of RNA viruses, and the unknown antigen presentation ability of dendritic cells with respect to nucleic acids. At the same time, there is no doubt that oligonucleotide vaccines based on highly conserved regions of the RNA virus genomes have great potential in the prevention of viral diseases, despite the fact that they do not yet fit within the framework of modern concepts of immunology [125].…”