[Allergen-specific immunotherapy utilizing mechanisms for immune regulation].

In Europe and America, the allergen immunotherapy (AIT) for various hay fevers or allergic rhinitis is enforced as causal treatment methods. However, in Japan, the only AIT is subcutaneous immunotherapy (SCIT) for Japanese cedar pollinosis and not so popular due to the long term treatment and the obscure mechanism of action being elucidated etc. We are now advancing research of the new vaccine technologies which aim at the practical applications of ASIT to Japanese cedar pollenosis. The first candidate vaccine is immunoregulatory liposomes which include antigenic polypeptides and chemicals for the induction of immunoregulatory cells such as invariant natural killer T (iNKT) cells, regulatory dendritic cells and regulatory T (Treg) cells. The liposomes encapsulated ovalbumin (OVA) were prepared and injected intraperitoneally into mice primed with alum-adsorbed OVA. After subsequent challenge with OVA alone, IgE and IgG antibody responses were remarkably suppressed for several months. The results suggest that the immunoregulatory liposomes containing antigenic polypeptides might suppress on-going IgE antibody formations during the pollen-season and induce long-term immune tolerance after the treatment. To elucidate the mechanism of action, next, the spleen cells of the mice treated with the immunoregulatory liposomes were analyzed. As a result, the liposomes were taken into B cells such as marginal zone B (MZB) cells in addition to the dendritic cells or the macrophages. It is demonstrated that IL-10 production after the interaction of the liposomes-captured B cells with iNKT cells are involved in the induction of Treg cells. Now, as a vaccine of Japanese cedar pollenosis, the immunoregulatory liposomes encapsulating the designed recombinant Cryj 1-Cryj 2 fusion protein is manufactured so that there may be no risk of anaphylaxis. In a mouse model sensitized with natural Cry j1 and Cry j2 antigens, the vaccine showed the suppression of IgE and IgG antibody responses after the challenge with the antigens. Moreover, oral administration of the vaccine also showed the efficacy for the IgE antibody suppression. Taken together, it is suggested that our basic technology for immunoregulatory liposomes can be applicable for any allergen-specific immunotherapies.