Impact of Ribosome Activity on SARS-CoV-2 LNP – Based mRNA Vaccines

Abstract

Coronavirus-related Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) initially was detected in Wuhan, Hubei, China. Since early 2021, World Health Organization (WHO) has declared Coronavirus Disease 2019 (COVID-19) a pandemic due to rapidly transformed to a globally massive catastrophic viral infection. In order to confront this emergency situation, many pharmaceutical companies focused on the design and development of efficient vaccines that are considered necessary for providing a level of normalization in totally affected human social-economical activity worldwide. A variety of vaccine types are under development, validation or even some of them have already completed these stages, initially approved as conditional marketing authorisation by Food and Drug Administration (FDA), European Medicines Agency (EMA), and other national health authorities for commercial purposes (in vivo use in general population), accelerating their production and distribution process. Innovative nucleoside-modified viral messenger RNA (v-mRNA)—based vaccines encapsulated within nanoparticles—specifically lipid ones (LNPs)—are now well recognized. Although this is a promising genetic engineering topic in the field of nanopharmacogenomics or targeted nucleic vaccines, there are limited but continuously enriched in vivo data in depth of time regarding their safety, efficacy, and immune response. In the current paper we expand the limited published data in the field of ribosome machinery and SARS-CoV-2 mRNA fragment vaccines interaction by describing their functional specialization and modifications. Additionally, alterations in post-transcriptional/translational molecules and mechanisms that could potentially affect the interaction between target cells and vaccines are also presented. Understanding these mechanisms is a crucial step for the next generation v-mRNA vaccines development.

Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action

“…Animal experiments have shown that adenovirus-vector DNA can remain detectable for months after inoculation in transcriptionally active form 82 in contrast to rapidly degraded RNA 55 , 83 . Persistence of antigen expression may be a distinctive feature of adenovirus vector vaccines, and has been proposed to contribute to induction of sustained immune responses and long-lasting immunity (reviewed in 41 ).…”

From delta to Omicron: S1-RBD/S2 mutation/deletion equilibrium in SARS-CoV-2 defined variants

“…Understanding the molecular significance of these different viral strains is a crucial step for designing and implementing rational and effective anti-SARS-CoV-2 strategies. For this reason, many pharmaceutical companies worldwide invest in the development of monoclonal antibodies (mAbs) and vaccines based on different platforms including, DNA plasmid based and also innovative nucleoside-modified viral messenger RNA encapsulated within nanoparticles -specifically lipid ones (LNPs) ( Lee et al, 2020 , Tsiambas et al, 2021 , Jackson et al, 2020 ). Efficient vaccines and mAbs are considered necessary in order normalization and restoration of disrupted global human social-economical activity to be established ( Flanagan et al, 2020 ; Dai et al, 2020).…”

Role of ribosomal pathways and comorbidity in COVID-19: Insight from SARS-CoV-2 proteins and host proteins interaction network analysis

“…The downregulation of these genes may impair the ribosome biogenesis process and affect protein synthesis [ 44 ]. This may have various effects on the body, including a decrease in the production of immune-related proteins and an impairment in the response to viral infections [ 45 ]. Additionally, these hub genes have been associated with various biological processes, including translation, cytoplasmic translation, mRNA splicing, and rRNA processing.…”