A sublingual vaccine strategy based on tablet delivery of molecular assemblies

Vaccines have been a revolutionary intervention for infectious diseases over the past many decades. However, over 2 million people continue to die every year of vaccine-preventable causes, especially in low-resource areas. This is mainly due to inefficiencies in the vaccine supply chain which in entirety lead to loss of potency of vaccines worth over $250 million every year due to temperature fluctuations. Additionally, vaccines that actually reach users may lose effectiveness because of more challenges related to their direct delivery to the recipients; for example, contamination and injuries from misuse of needles. We sought to take a step in addressing these challenges by developing thermally stable vaccine tablets for the sublingual delivery of self-assembled peptide nanofibers. Tablets were engineered from a combination of supramolecular peptide nanofibers plus the excipients, dextran and mannitol. The tablet structure was characterized to assess the impact of tablet formation on the nanofiber structure, as well as for suitability of sublingual delivery. In vivo studies were then carried out in a mouse model to determine the capacity to raise antigen-specific immunogenic responses. Sublingual delivery of the tablet in the mouse model was achieved and an immunogenic response was raised in mice. This proof-of-concept study indicates a step towards improving vaccines with regard to addressing challenges of the vaccine supply chain and vaccine delivery, especially in low resource centers.