Intranasally Administered Antigen 85B Gene Vaccine in Non-Replicating Human Parainfluenza Type 2 Virus Vector Ameliorates Mouse Atopic Dermatitis

Kitagawa, Hiroshi; Kawano, Mitsuo; Yamanaka, Keiichi; Kakeda, Masato; Tsuda, Kenshiro; Inada, Hiroyasu; Yoneda, Misao; Sakaguchi, Tadashi; Nigi, Akina; Nishimura, Koumei; Komada, Hiroshi; Tsurudome, Masato; Yasutomi, Yasuhiro; Nosaka, Tetsuya; Mizutani, Hitoshi

Atopic dermatitis (AD) is a refractory and recurrent inflammatory skin disease. Various factors including heredity, environmental agent, innate and acquired immunity, and skin barrier function participate in the pathogenesis of AD. T -helper (Th) 2-dominant immunological milieu has been suggested in the acute phase of AD. Antigen 85B (Ag85B) is a 30-kDa secretory protein well conserved in Mycobacterium species. Ag85B has strong Th1-type cytokine inducing activity, and is expected to ameliorate Th2 condition in allergic disease. To perform Ag85B function in vivo, effective and less invasive vaccination method is required. Recently, we have established a novel functional virus vector; recombinant human parainfluenza type 2 virus vector (rhPIV2): highly expressive, replication-deficient, and very low-pathogenic vector. In this study, we investigated the efficacy of rhPIV2 engineered to express Ag85B (rhPIV2/Ag85B) in a mouse AD model induced by repeated oxazolone (OX) challenge. Ear swelling, dermal cell infiltrations and serum IgE level were significantly suppressed in the rhPIV2/Ag85B treated mouse group accompanied with elevated IFN-γ and IL-10 mRNA expressions, and suppressed IL-4, TNF-α and MIP-2 mRNA expressions. The treated mice showed no clinical symptom of croup or systemic adverse reactions. The respiratory tract epithelium captured rhPIV2 effectively without remarkable cytotoxic effects. These results suggested that rhPIV2/Ag85B might be a potent therapeutic tool to control allergic disorders.