Epicutaneous immunization with protein antigen TNP-Ig and NOD2 ligand muramyl dipeptide (MDP) reverses skin-induced suppression of contact hypersensitivity

Background: epicutaneous (ec) immunization offers a new method of a needle-free and self-administrable immunization by using a topically applied patch to deliver vaccine. we have previously shown that ec immunization with hapten-conjugated protein antigen tnp-ig prior to hapten sensitization inhibits th1-mediated contact hypersensitivity (chs) in mice. our further work showed that ec immunization with tnp-ig and toll-like receptor (tlr) ligands prior to hapten sensitization reverses skin-induced suppression. methods: animal model of contact hypersensitivity was used to study reversal of skin-induced suppression. results: current work showed that ec immunization with protein antigen tnp-ig and mdp nod2 agonist - muramyldipeptide (l isoform) reverses skin-induced suppression of chs. on the other hand l18-mdp nod2 agonist - muramyldipeptide with a c18 fatty acid chain and mdp control - negative control for mdp - muramyldipeptide (d isoform,inactive) did not reverse skin-induced suppression. transfer in experiment showed that reversal of skin-induced suppression can be adoptively transferred with lymphoid cells isolated from donors ec treated with tnp-ig and mdp nod2 agonist. moreover,experiment employing two non-cross-reacting antigens tnp-ig and ox-ig proved that reversal of skin-induced suppression is antigen specific. additionally,lymph node cells isolated from mice ec immunized with tnp-ig and mdp nod2 agonist produced increased level of ifn-g suggesting that this cytokine might be involved in reversal of skin-induced suppression. conclusion: this work shows that ec immunization with protein antigen plus nod2 ligand mdp may be a potential tool to increase the immunogenicity of weekly immunogenic antigens. © 2014 institute of pharmacology,polish academy of sciences. published by elsevier urban & partner sp. z o.o. all rights reserved.