P-FN12, an H4R-Based Epitope Vaccine Screened by Phage Display, Regulates the Th1/Th2 Balance in Rat Allergic Rhinitis

摘要

Allergic rhinitis (AR) involves antigen-specific immune-inflammation of the nasal mucosa. Classical therapy for AR targets the histamine pathway, e.g., histamine receptor blockers. Histamine H4 receptor (H4R) was suggested as a novel therapeutic target due to its wide expression on almost all immune-related cells. A 12-mer random peptide library was used to select the specific epitope of the H4R. The phage clone showing the highest degree of activation was verified and translated to the corresponding peptide. The peptide FNKWMDCLSVTH, designated as P-FN12, was bound by H4R monoclonal antibody (mcAb) with high affinity. Moreover, the P-FN12?+ CTB@Lipo-formulated vaccine, used as nasal drops, decreased allergic symptoms such as sneezing and nasal rubbing in a rat model. The level of ovalbumin (OVA)-specific immunoglobulin E (IgE) decreased significantly after vaccine administration. It also elicited increased levels of interferon (IFN)-γ and interleukin-2 (IL-2) but a decreased level of IL-4, and it elevated the T helper type 1 (Th1):T helper type 2 (Th2) cell ratio in peripheral blood mononuclear cell cultures. Our results indicated that the reduction of allergic inflammation by P-FN12-based vaccine was related to a decrease in production of OVA-specific IgE,?Th2 immunity, and tissue eosinophilia. P-FN12?+ CTB@Lipo is a promising vaccine that could suppress Th2 response and enhance the induction of Th1 cells in an AR model.