mRNA-based vaccines have become an increasingly attractive platform to fight the ongoing SARS-CoV-2 pandemic for a multitude of reasons. Firstly, the need for only a DNA template of the desired antigen to produce a vaccine candidate, resulting in an exceedingly fast manufacturing timeline [
4]. Clinical testing of the first mRNA vaccine candidate (mRNA-1273) began on March 2020 [
74], just 66 days after the SARS-CoV-2 sequence was publicly released on January 2020 [
75], with the second candidates (BNT162b1 and BN162b2) entering into phase 1/2 clinical trials only a month later [
76,
77]. By contrast, the development of vaccine candidates utilizing traditional vaccine platforms has been lengthy because of the inherently slow nature of developing cell lines, generating virus, and/or producing clinical-grade protein subunits, as demonstrated by the fact that the only vaccines that have been granted emergency authorization by the FDA thus far are mRNA vaccines.
Secondly, mRNA vaccines elicited a very potent immune response in both animal studies and human clinical trials, as extensively discussed in
Section 3 and
Section 4. Importantly, these potent immune responses are substantiated by an impressive protection from COVID-19 in phase 2/3 studies [
10,
16]. While the FDA has initially stated that SARS-CoV-2 vaccines will require a minimum of 50% efficacy to qualify for approval [
78], both of the current mRNA vaccines currently approved for emergency use authorization (mRNA-1273 and BNT162b2) reported a greater than 94% efficacy [
10,
16]. This level of efficacy sets a very high standard for SARS-CoV-2 vaccines, considering that the next most-advanced vaccine candidate in clinical trials (ChAdOx1 nCoV-19), an adenoviral vector vaccine from AstraZeneca/University of Oxford, is only about 70% effective [
79].
mRNA vaccines also possess additional desirable features. Compared to other vaccine platforms, mRNA vaccines are appealing because of their minimalist nature. mRNA vaccines do not need a vector for their delivery/expression, thus removing the possible complication of pre-existing and/or de novo anti-vector immunity [
80]. Differently from inactivated or attenuated vaccines, less important antigenic targets that do not lead to nAb generation are not included. Since there is no need for the involvement of any viral growth, the possibility of other contaminating viruses from the cell lines is removed. mRNA vaccines that are encapsulated in LNPs also do not require complex delivery methods involving electroporation, as required by DNA vaccines, nor do they need the addition of an adjuvant, which is required with protein vaccines. Moreover, as described earlier, all available data suggest that the mRNA-LNP platform polarizes T cells towards a Th1 bias, suggesting that the likelihood of these vaccines causing adverse events, such as VAERD (discussed in
Section 3.2.2), seems quite remote.
Finally, mRNA vaccines can be readily modified based on need. Target immunogenic epitopes can be easily switched in and out of candidates, as all that is needed is the DNA sequence of the antigen to serve as a template. A SARS-CoV-2 vaccine construct can be quickly adjusted to target a newly emerged coronavirus strain [
8].