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Interleukin-1 Family Cytokines as Mucosal Vaccine Adjuvants for Induction of Protective Immunity against Inﬂuenza Virus (cid:1)

A safe and potent adjuvant is needed for development of mucosal vaccines against etiological agents, such as inﬂuenza virus, that enter the host at mucosal surfaces. Cytokines are potential adjuvants for mucosal vaccines because they can enhance primary and memory immune responses enough to protect against some infectious agents. For this study, we tested 26 interleukin (IL) cytokines as mucosal vaccine adjuvants and compared their abilities to induce antigen (Ag)-speciﬁc immune responses against inﬂu- enza virus. In mice intranasally immunized with recombinant inﬂuenza virus hemagglutinin (rHA) plus one of the IL cytokines, IL-1 family cytokines (i.e., IL-1 (cid:1) , IL-1 (cid:2) , IL-18, and IL-33) were found to increase Ag-speciﬁc immunoglobulin G (IgG) in plasma and IgA in mucosal secretions compared to those after immunization with rHA alone. In addition, high levels of both Th1- and Th2-type cytokines were observed in mice immunized with rHA plus an IL-1 family cytokine. Furthermore, mice intranasally immunized with rHA plus an IL-1 family cytokine had signiﬁcant protection against a lethal inﬂuenza virus infection. Interestingly, the adjuvant effects of IL-18 and IL-33 were signiﬁcantly decreased in mast cell-deﬁcient W/W v mice, indicating that mast cells have an important role in induction of Ag-speciﬁc mucosal immune responses induced by IL-1 family cytokines. In summary, our results demonstrate that IL-1 family cytokines are potential mucosal vaccine adjuvants and can induce Ag-speciﬁc immune responses for protection against pathogens like inﬂuenza virus.