mRNA technology as one of the promising platforms for the SARS-CoV-2 vaccine development

Abstract

After the genome sequence of SARS-CoV-2 (Severe acute respiratory syndrome-related coronavirus 2) was published and the number of infected people began to increase rapidly, many global companies began to develop a vaccine. Almost all known approaches to vaccine design were applied for this purpose, including inactivated viruses, mRNA and DNA-vaccines, vaccines based on various viral vectors, synthetically generated peptides and recombinant proteins produced in cells of insects and mammals. This review considers one of the promising vaccine platforms based on messenger RNA. Until recent years, mRNA-vaccination was out of practical implementation due to high sensitivity to nuclease degradation and consequent instability of drugs based on mRNA. Latest technological advances significantly mitigated the problems of low immunogenicity, instability, and difficulties in RNA-vaccine delivery. It is worth noting that mRNA-vaccines can efficiently activate both components of the immune system, i. e. T-cell and humoral responses. The essential advantage of mRNA-vaccines includes fast, inexpensive, scalable and uniform production providing a large output of desirable products in vitro. Synthesis and purification processes significantly simplify the process technology of mRNA drugs with injectable purity. Thus, mRNA production via in vitro transcription is more advantageous as compared with DNA-vaccines since it is a chemical process without the use of cells. mRNA techniques make it possible to pass all the phases of vaccine development much faster in comparison with the production of vaccines based on inactivated viruses or recombinant proteins. This property is critically important when designing vaccines against viral pathogens as the main problem of disease control includes a time gap between an epidemic and vaccine development. This paper discusses studies on the development of vaccines against coronaviruses including SARS-CoV-2 with special attention to the mRNA technique.

RNA modification in mRNA cancer vaccines

“…Firstly, mRNA vaccines have the excellent safety. Unlike DNA and viral vaccines, mRNA is a non-infectious nucleic acid substance and once delivered to the cytoplasm, the mRNA is translated immediately [ 61 , 126 ]. Since mRNA vaccines do not enter the nucleus and cannot integrate into the genome, there is no risk of causing genetic mutations in recipients [ 61 , 126 ].…”

“…Unlike DNA and viral vaccines, mRNA is a non-infectious nucleic acid substance and once delivered to the cytoplasm, the mRNA is translated immediately [ 61 , 126 ]. Since mRNA vaccines do not enter the nucleus and cannot integrate into the genome, there is no risk of causing genetic mutations in recipients [ 61 , 126 ]. Like native mRNAs, the activity of in vitro transcribed mRNAs is transient, and they are fully degraded by physiological metabolic pathways [ 61 ].…”

Immune response against DNA- and mRNA vaccines encoding artificial influenza virus immunogens

“…Существуют разные подхо-ды, направленные на разработку универсальной вакцины от гриппа. К ним относится, например, создание рекомбинантных белков-иммуногенов, использование консервативных фрагментов белков вируса гриппа (стебель гемагглютинина, белки NP, PB1, М1 и M2) или разработка новых типов вакцин на основе мРНК [2,3,4,5,7,8,9].…”

“…Помимо ДНК-вакцин, в последние 3-4 года активно развивается другой вид вакцин на основе нуклеиновых кислот, основанных на мРНК [3,4,10]. Данный тип вакцин обладает существенным преимуществом перед другими типами вакцин, в том числе и ДНК-вакцинами.…”

Construction and Immunogenicity of Modified mRNA-Vaccine Variants Encoding Influenza Virus Antigens

“…Many studies [ 18 , 19 ] have demonstrated that mRNA-based vaccines are a promising platform with such useful features as flexibility, scalability, cheap production, and independence from the cold chain [ 15 ]. Due to the possibility of making a simple change to the target gene in an mRNA vaccine without modifying production technology, one can quickly respond to the emergence of new pandemic infectious agents, especially the influenza virus.…”