The mucosal vaccine quandary Intranasal vs. sublingual immunization against influenza

Intranasal vaccination can effectively induce both local and systemic immune responses and protect against influenza, but poses a risk of antigen or adjuvant delivery into the central nervous system (CNS). Sublingual vaccine delivery has recently received increased attention as a safer alternative to the intranasal route. Studies comparing the two routes have found that higher immune responses may be induced by intranasal than sublingual administration, possibly as a consequence of the differences in mucosal tissues between the two routes. Here we examine evidence of antigen transport into the CNS following intranasal immunization and discuss possible reasons for the superiority of the intranasal as compared with the sublingual route in terms of vaccine immunogenicity. We encourage generation of more information on the safety of mucosal adjuvants and propose that the next generation of vaccines and adjuvants may be designed specifically for administration via the different mucosal routes.