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

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.

Anti-coronavirus vaccines will not accelerate the transition of humanity to a non-pandemic period, but the pandemic will take fewer victims.

The vaccination rate worldwide has reached enormous proportions, and it is likely that at least 75% of the world's population will be vaccinated. The controversy is that, while people aged 65 and older suffer a significantly higher mortality rate from COVID-19, plans are being made to vaccinate young people under the age of 20. Equally thorny is the question of vaccinating people who already have antibodies to SARS-CoV-2, as well as B and T memory cells, because they contracted and survived the virus. The possible consequences of large-scale vaccination are difficult to predict, when some people do not have access to the vaccine at all and others have already received 3 doses of the vaccine. SARS-CoV-2 will circulate through the human population forever and continue to mutate, as viruses do. Therefore, in the coming years, the need to develop and use effective vaccines and medicines for the prevention and treatment of COVID-19 will remain urgent in view of the high mortality rate from this disease. To date, three vaccine platforms have been most used: adenoviral vector, inactivated, and mRNA. There is some concern about the side effects that occur after vaccination. Whether modern anti-coronavirus vaccines can raise the safety threshold, only time will answer. It is obvious that the pandemic will end, but the virus will remain in the human population, leaving behind invaluable experience and tens of millions of victims. This article is based on search retrieves in research articles devoted to COVID-19 mainly published in 2020-2021 and examines the possible consequences of the worldwide vaccination against SARS-CoV-2 and suggests that, while anti-coronavirus vaccines will not magically transport humanity to a non-pandemic world, they may greatly reduce the number of victims of the pandemic and help us learn how to live with COVID-19.

SARS-CoV-2 will constantly sweep its tracks: a vaccine containing CpG motifs in 'lasso' for the multi-faced virus.

During the current COVID-19 pandemic, the global ratio between the dead and the survivors is approximately 1 to 10, which has put humanity on high alert and provided strong motivation for the intensive search for vaccines and drugs. It is already clear that if we follow the most likely scenario, which is similar to that used to create seasonal influenza vaccines, then we will need to develop improved vaccine formulas every year to control the spread of the new, highly mutable coronavirus SARS-CoV-2. In this article, using well-known RNA viruses (HIV, influenza viruses, HCV) as examples, we consider the main successes and failures in creating primarily highly effective vaccines. The experience accumulated dealing with the biology of zoonotic RNA viruses suggests that the fight against COVID-19 will be difficult and lengthy. The most effective vaccines against SARS-CoV-2 will be those able to form highly effective memory cells for both humoral (memory B cells) and cellular (cross-reactive antiviral memory T cells) immunity. Unfortunately, RNA viruses constantly sweep their tracks and perhaps one of the most promising solutions in the fight against the COVID-19 pandemic is the creation of 'universal' vaccines based on conservative SARS-CoV-2 genome sequences (antigen-presenting) and unmethylated CpG dinucleotides (adjuvant) in the composition of the phosphorothioate backbone of single-stranded DNA oligonucleotides (ODN), which can be effective for long periods of use. Here, we propose a SARS-CoV-2 vaccine based on a lasso-like phosphorothioate oligonucleotide construction containing CpG motifs and the antigen-presenting unique ACG-containing genome sequence of SARS-CoV-2. We found that CpG dinucleotides are the most rare dinucleotides in the genomes of SARS-CoV-2 and other known human coronaviruses, and hypothesized that their higher frequency could be responsible for the unwanted increased lethality to the host, causing a 'cytokine storm' in people who overexpress cytokines through the activation of specific Toll-like receptors in a manner similar to TLR9-CpG ODN interactions. Interestingly, the virus strains sequenced in China (Wuhan) in February 2020 contained on average one CpG dinucleotide more in their genome than the later strains from the USA (New York) sequenced in May 2020. Obviously, during the first steps of the microevolution of SARS-CoV-2 in the human population, natural selection tends to select viral genomes containing fewer CpG motifs that do not trigger a strong innate immune response, so the infected person has moderate symptoms and spreads SARS-CoV-2 more readily. However, in our opinion, unmethylated CpG dinucleotides are also capable of preparing the host immune system for the coronavirus infection and should be present in SARS-CoV-2 vaccines as strong adjuvants.

DNA insecticides: Data on the trial in the field.

This data article is related to the research articles entitled "The RING for gypsy moth control: topical application of fragment of its nuclear polyhedrosis virus anti-apoptosis gene as insecticide" (Oberemok et al., 2016), "Molecular alliance of Lymantria dispar multiple nucleopolyhedrovirus and a short unmodified antisense oligonucleotide of its anti-apoptotic IAP-3 gene: a novel approach for gypsy moth control" (Oberemok et al., 2017), and "Topical treatment of LdMNPV-infected gypsy moth caterpillars with 18 nucleotides long antisense fragment from LdMNPV IAP-3 gene triggers higher levels of apoptosis in infected cells and mortality of the pest" (Oberemok et al., 2017). This data article reports on the significant decrease of survival of L. dispar larvae after contact application of 18 nucleotides long antisense oligoRING fragment in the field experiment and supports perspective of use of DNA insecticides in forests.