Towards the future exploration of mucosal mRNA vaccines against emerging viral diseases; lessons from existing next-generation mucosal vaccine strategies

Abstract

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.

Immunogenicity and protective efficacy of GBP510/AS03 vaccine against SARS-CoV-2 delta challenge in rhesus macaques

“…GBP510/AS03 vaccination was shown here to be highly protective against challenge with Delta SARS-CoV-2 in rhesus macaques, correlating with antibody responses. Neutralizing antibody responses have been considered a correlate of protection for other COVID-19 vaccines, but further research of local immune responses is warranted 11,12,31,39 . In particular, future research should focus on the induction of mucosal antibody responses [40][41][42][43][44] as well as resident cellular responses [40][41][42][43][44][45] .…”

DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice

“…These achievements were reached through successive and iterative progress, both in mRNA delivery through LNP vehicles and in mRNA design. It has been widely documented that mRNA vaccine technology is easy- and fast-to-produce, cost-effective, and highly versatile, offering new perspectives to treat a large number of pathologies [ 43 , 44 , 45 ]. As global warming offers more suitable conditions to improve pathogen dissemination, human adaptation, and epidemic outbreak, mRNA vaccines will become a unique tool to propose a fast preventive deployment strategy onsite to interfere with new fast-adapting and -spreading human pathogens [ 46 , 47 ].…”

Development of Nasal Vaccines and the Associated Challenges

“…Cationic cyclodextrin-PEI conjugated to the IVT mRNA encoding OVA, significantly promoted nasal mRNA vaccine delivery in mice after nasal vaccination and also stimulated DC maturation and migration, which further enhanced the humoral and cellular immune responses [ 182 ]. The advent of mRNA vaccines against SARS-CoV-2 may further facilitate the development of lipid nanoparticle nasal mucosal RNA vaccines against respiratory infectious diseases [ 183 ]. This suggests that liposomes could be used for delivering several forms of antigens.…”