Epicutaneous immunization converts subsequent and established antigen‐specific T helper type 1 (Th1) to Th2‐type responses

Abstract

Epicutaneous immunization is a potential novel technique for topical vaccine delivery. It targets the immunologically rich milieu of the skin while having the advantage of being a non-invasive immunization procedure. By disrupting the stratum corneum of the epidermis a natural adjuvant effect can be achieved through activation of resident Langerhans cells. This negates the normal need for co-application of noxious adjuvants. Epicutaneous immunization on barrier-disrupted skin induces potent antigen-specific systemic immunity with a strong T helper type 2 (Th2) bias. We show here that epicutaneous immunization enhances the vigour of a subsequent T-cell response to the same antigen. The induced systemic Th2 response prevents the development of Th1 responses induced through injection of antigen in complete Freund's adjuvant (CFA). Prior epicutaneous immunization results in reduced production of antigen-specific interferon-gamma and immunoglobulin G2a (IgG2a) and enhanced interleukin-4, IgG1 and IgE responses to immunization with CFA. Moreover, epicutaneous immunization converts an established Th1 response to a Th2 response, as demonstrated by the specific reduction of interferon-gamma and IgG2a and the enhancement of interleukin-4 and IgE. This Th2 dominance of epicutaneous immunization may have direct therapeutic application as an immune-modulating procedure in Th1-dominant diseases such as autoimmune rheumatoid arthritis, type 1 diabetes, Hashimoto's thyroiditis and multiple sclerosis.