Evaluation of the quality, safety and efficacy of messenger RNA vaccines for the prevention of infectious diseases: regulatory considerations

Overview

Although the immunostimulatory effects of RNA have been known since the early 1960s (1), the possibility of using direct in vivo administration of in vitro transcribed messenger RNA (mRNA) to temporarily introduce genes expressing proteins (including antigens) was demonstrated in 1990 following the direct injection of “naked” nucleic acids (2). Subsequent improvements in stabilizing mRNA, increasing the feasibility of manufacturing RNA-based products and decreasing RNA-associated inflammatory responses have led to significant advances in the development of mRNA vaccines and therapeutics (3–6). There are several reasons why the mRNA platform has emerged at the forefront of vaccine technology. Among these are the rapid speed at which mRNA candidate vaccines can be constructed and manufactured, and the need to rapidly develop vaccines against emerging pathogens, such as zoonotic influenza virus strains, Zika virus and most recently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19).