Abstract
BACKGROUND: Although mRNA-based vaccines have been in development for over two decades, their widespread use only emerged during the COVID-19 pandemic. The success of these vaccines has brought mRNA technology to the forefront of efforts to develop novel vaccines. However, as this is a rapidly evolving field, there is a need for a comprehensive and up-to-date overview of the current evidence base to guide further research and development. This study, therefore, systematically reviewed the literature on clinical trials using mRNA vaccines for infectious diseases other than COVID-19. METHODS: A systematic review of the literature, following the PRISMA 2020 guidelines, identified clinical trials in infectious diseases other than COVID-19. PubMed and ClinicalTrials.gov were screened for such clinical trials using search terms related to mRNA vaccines, and the results of the two independent searches were combined. Clinical trials using mRNA vaccines against either COVID-19 or non-communicable diseases were removed, as were duplicated studies. The remaining clinical trials were then stratified based on pathogen, status, and phase. RESULTS: Nine hundred and seventy-six clinical trials were identified, of which 83 met the inclusion criteria. These included candidate mRNA vaccines against 14 viral, two bacterial and one protozoan infection. Of these, 43 trials have concluded, 21 are active, and a further 12 are recruiting, with the remaining not yet recruiting, enrolling by invitation, or withdrawn. Of the 43 completed clinical trials, 26 were phase I trials, eight were phase I/II trials, three were phase II trials, and six were phase III trials. The clinical trials captured in this systematic review included combined vaccines, with two or more vaccines administered at the same time, and mRNA vaccines designed to encode pathogen structural components, in addition to pathogen-specific antibodies. CONCLUSION: This systematic review identified clinical trials investigating mRNA vaccine candidates against multiple infectious diseases, other than COVID-19, with the majority targeting viral infections. Despite the lack of long-term data, this systematic review suggests that these mRNA vaccine candidates are safe and effective with the potential to shape the field of preventive medicine. Beyond the prevention of infectious diseases, mRNA vaccines are showing promise against cancer and potential applications in autoimmune and other diseases.