Interleukin-1 Family Cytokines as Mucosal Vaccine Adjuvants for Induction of Protective Immunity against Influenza Virus
Interleukin-1 Family Cytokines as Mucosal Vaccine Adjuvants for Induction of Protective Immunity against Influenza Virus
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DOI：
10.1128/jvi.01182-10
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发表时间：
2010-12-01
影响因子：
5.4
通讯作者：
Tsunoda, Shin-Ichi
中科院分区：
文献类型：
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作者：
Kayamuro, Hiroyuki;Yoshioka, Yasuo;Tsunoda, Shin-Ichi
需要一种安全而有效的佐剂来开发针对病原体的黏膜疫苗，例如流感病毒，这些病毒通过粘膜表面进入宿主。细胞因子是粘膜疫苗的潜在佐剂，因为它们可以增强初级和记忆免疫反应，足以保护某些感染性物质。在这项研究中，我们测试了26种白介素类细胞因子作为黏膜疫苗佐剂，并比较了它们诱导针对流感病毒的抗原(Ag)特异性免疫反应的能力。在重组流感病毒血凝素(RHA)加IL细胞因子之一的IL-1家族细胞因子(IL-1α、IL-1β、IL-18和IL-33)鼻腔免疫的小鼠中，与仅用RHA免疫的小鼠相比，血浆中的抗原特异性免疫球蛋白G(Ig G)和粘膜分泌物中的Ig A均显著升高。此外，在RHA加IL-1家族细胞因子免疫的小鼠中观察到高水平的Th1和Th2型细胞因子。此外，用RHA和IL-1家族细胞因子鼻腔免疫的小鼠对致死性流感病毒感染有显著的保护作用。有趣的是，在肥大细胞缺陷的W/W-v小鼠中，IL-18和IL-33的佐剂效应显著降低，表明肥大细胞在诱导IL-1家族细胞因子诱导的Ag特异性粘膜免疫反应中起着重要作用。综上所述，我们的结果表明，IL-1家族细胞因子是潜在的粘膜疫苗佐剂，可以诱导抗原特异性免疫反应，从而保护机体免受流感病毒等病原体的侵袭。
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 influenza 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 alpha, IL-1 beta, 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.