The mRNA vaccine platform has offered the greatest potential in fighting the COVID-19 pandemic owing to rapid development, effectiveness, and scalability to meet the global demand. There are many other mRNA vaccines currently being developed against different emerging viral diseases. As with the current COVID-19 vaccines, these mRNA-based vaccine candidates are being developed for parenteral administration via injections. However, most of the emerging viruses colonize the mucosal surfaces prior to systemic infection making it very crucial to target mucosal immunity. Although parenterally administered vaccines would induce a robust systemic immunity, they often provoke a weak mucosal immunity which may not be effective in preventing mucosal infection. In contrast, mucosal administration potentially offers the dual benefit of inducing potent mucosal and systemic immunity which would be more effective in offering protection against mucosal viral infection. There are however many challenges posed by the mucosal environment which impede successful mucosal vaccination. The development of an effective delivery system remains a major challenge to the successful exploitation of mucosal mRNA vaccination. Nonetheless, a number of delivery vehicles have been experimentally harnessed with different degrees of success in the mucosal delivery of mRNA vaccines. In this review, we provide a comprehensive overview of mRNA vaccines and summarise their application in the fight against emerging viral diseases with particular emphasis on COVID-19 mRNA platforms. Furthermore, we discuss the prospects and challenges of mucosal administration of mRNA-based vaccines, and we explore the existing experimental studies on mucosal mRNA vaccine delivery.

In recent years, there has been ample evidence illustrating the effect of microbiota on gut immunity, homeostasis, and disease. Most of these studies have engaged more efforts in understanding the role of the bacteriome in gut mucosal immunity and disease. However, studies on the virome and its influence on gut mucosal immunity and pathology are still at infancy owing to limited metagenomic tools. Nonetheless, the existing studies on the virome have largely been focused on the bacteriophages as these represent the main component of the virome with little information on endogenous retroviruses (ERVs) and eukaryotic viruses. In this review, we describe the gut virome, and its role in gut mucosal response and disease progression. We also explore the crosstalk between the virome and other microorganisms in the gut mucosa and elaborate on how these interactions shape the gut mucosal immunity going from bacteriophages through ERVs to eukaryotic viruses. Finally, we elucidate the potential contribution of this crosstalk in the pathogenesis of inflammatory bowel diseases and colon cancer.