**4.1 Nucleic acid—based vaccine**

The nucleic acid vaccine depends on the delivery of the viral genetic codes rather than the viral protein; the transcription and translation processes performed by the host are used to encode the antigen inside the cell before its presentation through the class I of MHC. The technology is relatively new, and no approved nucleic acid vaccines have been used beyond the COVID-19.

### **4.2 BNT162b2 mRNA COVID-19 vaccine (Pfizer)**

BNT162b2 is a lipid nanoparticle–formulated [38], nucleoside-modified RNA expressing the full-length of spike gene, adapted by two proline modifications to keep its structure in the prefusion conformation. Two 30 ug doses of Pfizer vaccine produced significant neutralizing antibody titers directed against SARS-CoV-2, and particular CD8+ and CD4+ T cell responses in healthy individuals in trials done in the United States and Germany [39]. Furthermore, Pfizer vaccine's reactogenicity profile reflected minimal side effects. The development of the BNT162b2 vaccine into phase 3 was encouraged by these findings. The tolerability, safety, immunoreactivity, and efficacy of 30 μg of BNT162b2 in controlling COVID-19 were evaluated in individuals, which are 16 years old or older [40].

### **4.3 The mRNA-1273 SARS-CoV-2 vaccine (Moderna)**

The mRNA1273 vaccine is an mRNA-based lipid nanoparticle encapsulated vaccine expressing the fusion-stabilized full-length spike protein of (SARS-CoV-2) [40]. The moderna vaccine revealed 94.1% efficacy at stopping COVID-19 severity. mRNA-1273's efficacy is comparable to that of the previously disclosed BNT162b2 mRNA vaccination [41].
