Figures & data
Figure 1. Eukaryotic mRNA engaging in translation: a eukaryotic mRNA showing five structural components; 5’ cap, 5’ untranslated region (5’UTR), open reading frame (ORF), 3’UTR, and poly(A) tail. The 5’ cap – m [Citation7]G attached to the first nucleotide via a triphosphate bridge is shown. The 5’ cap structure along with first two nucleotides of the transcript was borrowed from [Citation28]. Engagement of the mRNA in translation is shown on the right. The mRNA gets circularized by indirect contact between 5’ cap and 3’ poly(A) tail with the assistance of poly(A) binding protein (PABP) and other translation initiation factors, as shown. Other translation initiation factors have not been shown for simplicity.
![Figure 1. Eukaryotic mRNA engaging in translation: a eukaryotic mRNA showing five structural components; 5’ cap, 5’ untranslated region (5’UTR), open reading frame (ORF), 3’UTR, and poly(A) tail. The 5’ cap – m [Citation7]G attached to the first nucleotide via a triphosphate bridge is shown. The 5’ cap structure along with first two nucleotides of the transcript was borrowed from [Citation28]. Engagement of the mRNA in translation is shown on the right. The mRNA gets circularized by indirect contact between 5’ cap and 3’ poly(A) tail with the assistance of poly(A) binding protein (PABP) and other translation initiation factors, as shown. Other translation initiation factors have not been shown for simplicity.](/cms/asset/a84c752b-c299-4061-9fd9-32f5eb18290e/ierv_a_2320327_f0001_oc.jpg)
Table 1. Common nucleotide modifications of mRNA vaccines.
Figure 2. In vitro production of mRNA vaccine and elicitation of immune response through transfection of antigen presenting cells [1]: after sequencing the genome of the pathogen, the sequence encoding the antigen of interest, flanked with 5’ and 3’ UTR sequences, is cloned in the plasmid downstream of the T7 promoter [2]. The purified plasmid is used as template in the in vitro T7 transcription reaction for the synthesis of mRNA encoding the antigen [3]. The mRNA is purified by high performance liquid chromatography (HPLC) and formulated into lipid nanoparticles (LNPs) for delivery [4]. The LNPs are filtered to remove the free mRNA [5]. The purified LNPs are stored in vials and used for vaccination [6]. Endocytosis of the LNP by antigen presenting cell in vaccinated individuals [7]. The mRNA escapes the endocytosed LNP and engages into translation in the cellular cytoplasm [8]. The translated antigen is broken down into small fragments by the proteosome and the resulting protein fragments are displayed on the surface of by major histocompatibility complex (MHC) class I molecules to activate cytotoxic T cells [9]. The activated cytotoxic T cell produces toxic molecules such as perforin and granzyme that target the infected cells [10]. The secreted antigen can be the cells, degraded and presented on the surface by MHC class II proteins to activate T helper cells [11]. Helper T cells activate the B cells to produce neutralizing antibodies for the clearance of the pathogen. Helper T cells also stimulate phagocytes such as macrophages by inflammatory cytokines.
![Figure 2. In vitro production of mRNA vaccine and elicitation of immune response through transfection of antigen presenting cells [1]: after sequencing the genome of the pathogen, the sequence encoding the antigen of interest, flanked with 5’ and 3’ UTR sequences, is cloned in the plasmid downstream of the T7 promoter [2]. The purified plasmid is used as template in the in vitro T7 transcription reaction for the synthesis of mRNA encoding the antigen [3]. The mRNA is purified by high performance liquid chromatography (HPLC) and formulated into lipid nanoparticles (LNPs) for delivery [4]. The LNPs are filtered to remove the free mRNA [5]. The purified LNPs are stored in vials and used for vaccination [6]. Endocytosis of the LNP by antigen presenting cell in vaccinated individuals [7]. The mRNA escapes the endocytosed LNP and engages into translation in the cellular cytoplasm [8]. The translated antigen is broken down into small fragments by the proteosome and the resulting protein fragments are displayed on the surface of by major histocompatibility complex (MHC) class I molecules to activate cytotoxic T cells [9]. The activated cytotoxic T cell produces toxic molecules such as perforin and granzyme that target the infected cells [10]. The secreted antigen can be the cells, degraded and presented on the surface by MHC class II proteins to activate T helper cells [11]. Helper T cells activate the B cells to produce neutralizing antibodies for the clearance of the pathogen. Helper T cells also stimulate phagocytes such as macrophages by inflammatory cytokines.](/cms/asset/414828a8-fd55-45e8-92c7-ff16a9f0ca83/ierv_a_2320327_f0002_oc.jpg)
Table 2. List of Major SARS-CoV-2 vaccine trials+.