mRNA Vaccines as an Efficient Approach for the Rapid and Robust Induction of Host Immunity Against SARS-CoV-2

Abstract

Among the currently used COVID-19 vaccines, the mRNA-based vaccines drew the interest of the scientists because of its potent and versatile nature in mitigating the disease efficiently through increased translation as well as the robust modulation of the innate and adaptive immune responses within the host. The naked or lipid encapsulated mRNAs are usually optimized in order to formulate the vaccine. One of the interesting advantage of using mRNA vaccines is that such platform can even be used to mitigate other infectious diseases like influenza, zika, and rabies. However, the leading COVID-19 mRNA vaccines, i.e., mRNA-1273 and BNT162b2, have already been noticed to possess around 95% efficacy in provoking both the humoral and cell mediated immunity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, causing the ongoing COVID-19 pandemic.

Keywords: COVID-19 mRNA vaccines; Immunity; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Vaccine efficiency; mRNA 1273 vaccine; mRNA BNT162b2 vaccine.

Fig. 1

Mode of action of vaccines based on RNA platform. In the inset, a scheme mRNA vaccine has been shown where the optimization of relevant codons (especially of the genes encoding spike proteins) is notable. UTR stands for the untranslated regions. The modification of the uridine is done, i.e., converted to N1-methyl-pseudouridine. The main diagram shows how mRNA vaccine facilitates the expression of the spike (S) protein. The mRNA which encodes the full-length S protein is encapsulated into a lipid nanoparticle (LNP) [3, 6, 12]. The encapsulated and in vitro synthesized mRNA enters the host through endocytosis, escapes the endosomal degradation, and translated to produce the S proteins. The nascent S proteins are transported into the lumen of the endoplasmic reticulum (ER) as in case of natural infection [12]. Later the exocytosis takes place, leading to expression of the spike proteins across the plasma membrane. This is to be noted that the intracellularly synthesized protein may undergo degradation within proteasome followed by the entry of the epitopes within the grooves of major histocompatibility complex (MHC) I and II thereby facilitating the antigenic peptide presentation by MHC I and MHC II which in turn, triggers the induction of cellular and humoral immunity, respectively [3, 6, 12]