COVID-19 mRNA vaccines: Platforms and current developments
Authors: Gábor Tamás Szabó, Azita Josefine Mahiny, Irena Vlatkovic
Journal: Molecular Therapy (2022)

Since the first successful application of messenger ribonucleic acid (mRNA) as a vaccine agent in a preclinical study nearly 30 years ago, numerous advances have been made in the field of mRNA therapeutic technologies. This research uncovered the unique favorable characteristics of mRNA vaccines, including their ability to give rise to non-toxic, potent immune responses and the potential to design and upscale them rapidly, making them excellent vaccine candidates during the coronavirus disease 2019 (COVID-19) pandemic. Indeed, the first two vaccines against COVID-19 to receive accelerated regulatory authorization were nucleoside-modified mRNA vaccines, which showed more than 90% protective efficacy against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alongside tolerable safety profiles in the pivotal phase III clinical trials. Real-world evidence following the deployment of global vaccination campaigns utilizing mRNA vaccines has bolstered clinical trial evidence and further illustrated that this technology can be used safely and effectively to combat COVID-19. This unprecedented success also emphasized the broader potential of this new drug class, not only for other infectious diseases, but also for other indications, such as cancer and inherited diseases. This review presents a brief history and the current status of development of four mRNA vaccine platforms, nucleoside-modified and unmodified mRNA, circular RNA, and self-amplifying RNA, as well as an overview of the recent progress and status of COVID-19 mRNA vaccines. We also discuss the current and anticipated challenges of these technologies, which may be important for future research endeavors and clinical applications. Since the first successful application of messenger ribonucleic acid (mRNA) as a vaccine agent in a preclinical study nearly 30 years ago, numerous advances have been made in the field of mRNA therapeutic technologies. This research uncovered the unique favorable characteristics of mRNA vaccines, including their ability to give rise to non-toxic, potent immune responses and the potential to design and upscale them rapidly, making them excellent vaccine candidates during the coronavirus disease 2019 (COVID-19) pandemic. Indeed, the first two vaccines against COVID-19 to receive accelerated regulatory authorization were nucleoside-modified mRNA vaccines, which showed more than 90% protective efficacy against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alongside tolerable safety profiles in the pivotal phase III clinical trials. Real-world evidence following the deployment of global vaccination campaigns utilizing mRNA vaccines has bolstered clinical trial evidence and further illustrated that this technology can be used safely and effectively to combat COVID-19. This unprecedented success also emphasized the broader potential of this new drug class, not only for other infectious diseases, but also for other indications, such as cancer and inherited diseases. This review presents a brief history and the current status of development of four mRNA vaccine platforms, nucleoside-modified and unmodified mRNA, circular RNA, and self-amplifying RNA, as well as an overview of the recent progress and status of COVID-19 mRNA vaccines. We also discuss the current and anticipated challenges of these technologies, which may be important for future research endeavors and clinical applications.