Mucosal Vaccination: A Promising Alternative Against Flaviviruses.

The Flaviviridae are a family of positive-sense, single-stranded RNA enveloped viruses, and their members belong to a single genus, Flavivirus. Flaviviruses are found in mosquitoes and ticks; they are etiological agents of: dengue fever, Japanese encephalitis, West Nile virus infection, Zika virus infection, tick-borne encephalitis, and yellow fever, among others. Only a few flavivirus vaccines have been licensed for use in humans: yellow fever, dengue fever, Japanese encephalitis, tick-borne encephalitis, and Kyasanur forest disease. However, improvement is necessary in vaccination strategies and in understanding of the immunological mechanisms involved either in the infection or after vaccination. This is especially important in dengue, due to the immunological complexity of its four serotypes, cross-reactive responses, antibody-dependent enhancement, and immunological interference. In this context, mucosal vaccines represent a promising alternative against flaviviruses. Mucosal vaccination has several advantages, as inducing long-term protective immunity in both mucosal and parenteral tissues. It constitutes a friendly route of antigen administration because it is needle-free and allows for a variety of antigen delivery systems. This has promoted the development of several ways to stimulate immunity through the direct administration of antigens (e.g., inactivated virus, attenuated virus, subunits, and DNA), non-replicating vectors (e.g., nanoparticles, liposomes, bacterial ghosts, and defective-replication viral vectors), and replicating vectors (e.g.,