Challenges and opportunities in the development of mucosal mRNA vaccines

mRNA vaccines have played a critical role in controlling the SARS-CoV-2 pandemic, and are being actively studied for use in other diseases. There is a growing interest in applying mRNA vaccines at mucosal surfaces as it enables access to a unique immune reservoir in a less-invasive manner. However, mucosal surfaces present several barriers to mRNA uptake, including degrading enzymes, mucus, and clearance mechanisms. In this mini-review, we discuss our understanding of the immune response to mucosal mRNA vaccines as it compares to systemic mRNA vaccines. We also highlight physical and chemical methods for enhancing mRNA uptake across mucosal tissues. Mucosal mRNA vaccination is a nascent field of research, which will greatly benefit from fundamental investigations into the mechanisms of immune activation and the development of technologies for improved delivery.