Vaccines on demand, part II: future reality

Prior to the emergence of SARS-CoV-2, the potential use of mRNA vaccines for a rapid pandemic response had been well described in the scientific literature, however during the SARS-CoV-2 outbreak we witnessed the large-scale deployment of the platform in a real pandemic setting. Of the three RNA platforms evaluated in clinical trials, including 1) conventional, non-amplifying mRNA (mRNA), 2) base-modified, non-amplifying mRNA (bmRNA), which incorporate chemically modified nucleotides, and 3) self-amplifying RNA (saRNA), the bmRNA technology emerged with superior clinical efficacy.

This review describes the current state of these mRNA vaccine technologies, evaluates their strengths and limitations, and argues that saRNA may have significant advantages if the limitations of stability and complexities of manufacturing can be overcome.

The success of the SARS-CoV-2 mRNA vaccines has been remarkable. However, several challenges remain to be addressed before this technology can successfully be applied broadly to other disease targets. Innovation in the areas of mRNA engineering, novel delivery systems, antigen design, and high-quality manufacturing will be required to achieve the full potential of this disruptive technology.