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Review
. 2021 Aug 31;11(9):907.
doi: 10.3390/life11090907.

Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2

Daniela Calina  1 , Antonio F Hernández  2   3   4 , Thomas Hartung  5   6 , Alexey M Egorov  7   8 , Boris Nikolaevich Izotov  9 , Taxiarchis Konstantinos Nikolouzakis  10 , Aristidis Tsatsakis  9   10 , Panayiotis G Vlachoyiannopoulos  11 , Anca Oana Docea  12
Affiliations
Review

Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2

Daniela Calina et al. Life (Basel). .

Abstract

In the context of the current COVID-19 pandemic, traditional, complex and lengthy methods of vaccine development and production would not have been able to ensure proper management of this global public health crisis. Hence, a number of technologies have been developed for obtaining a vaccine quickly and ensuring a large scale production, such as mRNA-based vaccine platforms. The use of mRNA is not a new concept in vaccine development but has leveraged on previous knowledge and technology. The great number of human resources and capital investements for mRNA vaccine development, along with the experience gained from previous studies on infectious diseases, allowed COVID-19 mRNA vaccines to be developed, conditionally approved and commercialy available in less than one year, thanks to decades of basic research. This review critically presents and discusses the COVID-19 mRNA vaccine-induced immunity, and it summarizes the most common anaphylactic and autoimmune adverse effects that have been identified until now after massive vaccination campaigns.

Keywords: COVID-19 pandemic; coronaviruses; mRNA vaccines; public health; side effects.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Diagram of the new concept of mRNA vaccines against SARS-CoV-2. Legend: deoxyribonucleic acid (DNA), messenger RNA (mRNA), ribonucleic acid (RNA).
Figure 2
Figure 2
The pharmacological mechanism of action of intramuscularly administered mRNA vaccines (I). The vaccine releases LNPs containing mRNA encoding S protein into the muscle cells. However, most of the LNPs are uptaken by dendritic cells which translate mRNA into protein, process and present the protein peptides binding them to MHC-I and MHC-II to naïve B and T cells in the regional lymph nodes. Legend: messenger RNA (mRNA), lipid nanoparticles (LNPs), major histocompatibility complex (MHC).
Figure 3
Figure 3
The pharmacological mechanism of action of intramuscularly administered mRNA vaccines (I). Dendritic cells travel through the lymphatic vessels and enter the lymph node by afferent lymph vessels. In addition, LNPs alone also enter the lymph node by afferent lymphatics, and they are uptaken by native macrophages of the lymph node. On the other hand, naïve B and T cells enter the lymph node by arterioles which inside the lymph node shift to high endothelial venules and provide ligands to transiently stop the flow of these cells which then, guided by chemokines, move into the lymph node. Dendritic cells and native macrophages of the lymph node process and present appropriately S protein-peptide fragments to naïve CD4+T, CD8+T and B cells which become armed effector T lymphocytes and plasma cells, respectively. Legend: inducible T cell costimulator (ICOS), ICOS ligand (ICOSL), high endothelial venules (HEV), chemokines (CCL), cluster differentiation (CD).
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