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

Daniela Calina,Antonio F Hernández,Boris Nikolaevich Izotov,Thomas Hartung,Anca Oana Docea,Alexey M Egorov,Taxiarchis Konstantinos Nikolouzakis,Panayiotis G Vlachoyiannopoulos,Aristidis Tsatsakis

doi:10.3390/life11090907

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.

Highlights

SARS-CoV-2 is an enveloped virus with a single-stranded RNA genome that belongs to the β-coronavirus family such that it is structurally and functionally similar to other members of this family, especially SARS-CoV [1,2]
The spike (S) glycoprotein in SARS-CoV-2 plays a pivotal role as a membrane fusion protein; it consists of two subunits with distinct functions: S1, which contains a receptorbinding domain (RBD) that recognizes and binds to the host cell receptor angiotensinconverting enzyme 2 (ACE2), and S2, which is essential for the virus–cell membrane fusion process
The new generation and the new concept of messenger RNA (mRNA) vaccines against SARS-CoV-2 by-pass the transcription of DNA to mRNA in the nucleus

Summary

Introduction

SARS-CoV-2 is an enveloped virus with a single-stranded RNA genome that belongs to the β-coronavirus family such that it is structurally and functionally similar to other members of this family, especially SARS-CoV ( called SARS-CoV-1) [1,2]. The immunodominant component of S protein, the RBD, is less conserved showing approximately 47% similarity between SARS-CoV and SARS-CoV-2 [1,11] This knowledge allowed us, based on previous experience with SARS-CoV and other coronaviruses, to propose methods for developing distinct vaccines against COVID-19 that may be safe and effective at preventing serious illness, hospitalization and COVID-19-related deaths [12,13]. The principles of messenger RNA (mRNA) vaccination techniques date back to the early 1990s [17], and dozens of studies on the subject have been published since During these three decades, significant progress has been made on how the mRNA molecule is constructed to be efficiently processed by cells, and how these molecules can be packaged to ensure protection from degradation on their way to target cells [18]. Any deviation from the tested protocol under current real-life conditions may result in mRNA degradation that accounts for a possible decrease in the vaccine efficiency by decreasing the amount of mRNA available [30]

The New Concept and Development of mRNA Vaccines against SARS-CoV-2

Pharmacological Mechanism of Action of mRNA Vaccines

Potential Secondary Reactions to mRNA Vaccines

Autoimmune Diseases and COVID-19: A Possible Tie-Up

Findings

Future Perspectives and Overall Conclusions