The clinical progress of mRNA vaccines and immunotherapies

• Published in: Nature biotechnology Vol. 40; no. 6; pp. 840 - 854
• Main Authors: Barbier, Ann J., Jiang, Allen Yujie, Zhang, Peng, Wooster, Richard, Anderson, Daniel G.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2022; Nature Publishing Group
• Subjects: 631/154/152; 631/208/2489/201/2110; 692/700/565/201; Agriculture; Bioinformatics; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Cancer; Coronaviruses; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines - therapeutic use; Epstein-Barr virus; Epstein-Barr Virus Infections; Herpesvirus 4, Human; HIV; Human immunodeficiency virus; Humans; Immunization, Secondary; Immunostimulation; Immunosuppressive agents; Immunotherapy; Infectious diseases; Influenza; Influenza Vaccines; Life Sciences; mRNA; mRNA Vaccines; Nucleic acids; Protein expression; Proteins; Respiratory diseases; Review Article; RNA, Messenger - genetics; Severe acute respiratory syndrome; Vaccines; Vaccines, Synthetic; Viral diseases
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/s41587-022-01294-2

The emergency use authorizations (EUAs) of two mRNA-based severe acute respiratory syndrome coronavirus (SARS-CoV)-2 vaccines approximately 11 months after publication of the viral sequence highlights the transformative potential of this nucleic acid technology. Most clinical applications of mRNA to date have focused on vaccines for infectious disease and cancer for which low doses, low protein expression and local delivery can be effective because of the inherent immunostimulatory properties of some mRNA species and formulations. In addition, work on mRNA-encoded protein or cellular immunotherapies has also begun, for which minimal immune stimulation, high protein expression in target cells and tissues, and the need for repeated administration have led to additional manufacturing and formulation challenges for clinical translation. Building on this momentum, the past year has seen clinical progress with second-generation coronavirus disease 2019 (COVID-19) vaccines, Omicron-specific boosters and vaccines against seasonal influenza, Epstein–Barr virus, human immunodeficiency virus (HIV) and cancer. Here we review the clinical progress of mRNA therapy as well as provide an overview and future outlook of the transformative technology behind these mRNA-based drugs. Anderson and colleagues discuss the progress and challenges of using mRNA for vaccines and immunotherapy.