Safety and efficacy of mRNA vaccines: a mechanistic and public health perspective.

Publication date: Jun 30, 2026

mRNA vaccines represent a transformative advance in vaccinology, combining rapid development timelines, scalable manufacturing, and strong immunogenicity with a favourable safety profile. Global deployment of mRNA vaccines during the COVID-19 pandemic provided an unprecedented real-world evaluation of this platform, with billions of doses administered across diverse populations. In this Review, we critically examine the safety and efficacy of mRNA vaccines from mechanistic, preclinical, clinical, and public health perspectives. We outline the biological basis of mRNA vaccines, including their transient cytoplasmic expression, lack of genomic integration, and rapid clearance, distinguishing them clearly from other gene therapies. We synthesise evidence on vaccine components, manufacturing quality controls, and regulatory standards that underpin safety, alongside data from randomised trials, post-authorisation surveillance, and active pharmacovigilance systems. We also review real-world effectiveness across age groups, pregnancy, and populations that are immunocompromised, along with the effects on transmission. Last, we address public perception and vaccine confidence, and discuss implications for next-generation mRNA vaccines, including strategies to reduce reactogenicity, improve breadth and durability of immunity, enhance global access, and support sustainable public trust. Together, the accumulated evidence affirms mRNA vaccines as a safe, effective, and adaptable platform with enduring relevance for future infectious disease prevention and public health preparedness, and for the treatment of cancer and autoimmunity.

Semantics

Original Article