LY2157299 Therefore, G9.1 appears to be a promising pDC-dependent POtype TH1-enhancing CpG ODN for a future mucosal vaccine. The principal advantage of mucosal vaccines is that antigens can be neutralized before systemic invasion. Although antitoxin activity was detected in the sera of G9.1-injected mice, we could not determine antitoxin activity directly in mucosal preparations owing to dilution of secretory fluid by the washing solution. Nonetheless, we provide evidence that G9.1 also induces DT-specific IgA secretions from mucous membranes of aerodigestive tracts. It is unclear how G9.1 enhances mucosal IgA production. One possibility is increased epithelial transport of IgA by IFN-cmediated upregulation of the polymeric immunoglobulin receptor because IFN-c is known to upregulate PIGR. It has also been demonstrated that the switching of uncommitted IgM+ B cells to IgA-expressing cells is directed by TGF-b1 and CD40L. Recently, Tezuka et al. reported that pDCs in gutassociated lymphatic tissue play a critical role in T cellindependent IgA production by expressing APRIL and BAFF, the TNF family ligands inducing IgA production. Our results also suggest that G9.1-induced BAFF production may contribute to upregulation of IgA production in the nasal DTvaccination system. No alteration in the level of TGF-b even by the culture with G9.1 may be ascribed to its constitutive production. The cells responsible for BAFF production are currently under investigation. Many vaccines cause allergic reactions in susceptible individuals, and use of CpG ODNs is a promising strategy to circumvent allergic responses. pDCs appear to suppress allergic responses through enhancement of TH1 immunity. G9.1 increased T-bet expression but did not decrease GATA-3 expression. However, the G9.1-mediated increase in IgG responses may reduce IgE responses, leading to suppression of allergic inflammation. Thus, vaccination with G9.1 may be particularly advantageous, not only to induce phylaxis, but also to control ongoing inflammation. The data supporting this notion are presented in the annex. Most protein antigens exhibit poor immunogenicity when administered mucosally and can even induce immunological tolerance. In addition, antigens administered mucosally must survive degradation by luminal enzymes and trapping by mucus. Therefore, much effort is currently being devoted to the development of an effective adjuvant that triggers protective immunity to combat infectious microbes at the mucosal surface. Given the demonstrated phylactic, TH1-inducing, and anti-allergic effects shown here, we propose G9.1 as a promising mucosal adjuvant for the development of novel vaccines, such as oral and nasal vaccines, to overcome emerging and re-emerging infectious diseases. The mechanisms for G9.1 adjuvanticity and optimal methods for mucosal vaccination warrant intensive study.