Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines.
Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines.
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DOI：
10.1016/j.ebiom.2016.11.015
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发表时间：
2017-02
期刊：
影响因子：
11.1
通讯作者：
Ishii KJ
中科院分区：
文献类型：
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作者：
Hayashi M;Aoshi T;Haseda Y;Kobiyama K;Wijaya E;Nakatsu N;Igarashi Y;Standley DM;Yamada H;Honda-Okubo Y;Hara H;Saito T;Takai T;Coban C;Petrovsky N;Ishii KJ
Advax是一种δ菊粉衍生的微粒，已被开发为几种疫苗的佐剂。然而，其免疫学特性和潜在的作用机制尚未阐明。在这里，我们表明，Advax的行为作为2型佐剂与流感裂解疫苗，辅助性T细胞（Th）2型抗原相结合时，但作为1型佐剂与流感灭活的全病毒粒子（WV），Th 1型抗原相结合时。此外，当Advax佐剂化的WV疫苗用于免疫不能对WV抗原中所含RNA应答的toll样受体（TLR）7敲除小鼠时，未观察到佐剂效应。同样，当Advax与无内毒素的卵清蛋白（一种中性Th 0型抗原）联合使用时，未观察到佐剂效应。在肿瘤坏死因子（TNF）-α敲除小鼠中也未观察到佐剂效应，并且佐剂效应需要树突状细胞（DC）和吞噬巨噬细胞的存在。因此，与其他佐剂不同，Advax增强了共同施用抗原的内在或内置佐剂性质。因此，Advax是一类独特的佐剂，可通过尚待确定的机制增强疫苗抗原的内在佐剂特征。Advax增强疫苗抗原的内在佐剂特性。Advax不改变疫苗抗原诱导的T辅助细胞免疫偏好。树突状细胞、吞噬巨噬细胞和肿瘤坏死因子-α在Advax佐剂活性中发挥作用。佐剂是使疫苗效力最大化的不可缺少的试剂。无论抗原的性质如何，大多数佐剂一致地将辅助性T细胞（Th）1、Th 2或Th 17偏向性赋予疫苗应答。例如，无论疫苗抗原如何，明矾佐剂始终赋予Th 2偏好。在这里，我们表明，δ菊粉衍生的微粒佐剂，Advax，是一个额外的一类佐剂，作为一个放大器的内置佐剂活性内的抗原本身的功能。Advax增强不同类型的适应性免疫反应，这取决于抗原自身的内置佐剂特性，证实了Advax作为通用疫苗佐剂的实用性。
Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF)-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs) and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism. Advax potentiates built-in adjuvant property of vaccine antigens. Advax does not change the T helper immune bias induced by the vaccine antigen. Dendritic cells, phagocytic macrophages, and tumor necrosis factor-α play a role in Advax adjuvant activity. Adjuvants are indispensable agent to maximize the efficacy of vaccines. Most adjuvants consistently impart either T helper (Th)1, Th2 or Th17 bias to the vaccine response regardless of the properties of antigen. For example alum adjuvants consistently impart a Th2 bias regardless of the vaccine antigen. Here we show that a delta inulin-derived microparticle adjuvant, Advax, is an additional class of adjuvant that functions as an amplifier of in-built adjuvant activity within the antigens themselves. Advax enhances different types of adaptive immune response dependent on the antigen's own in-built adjuvant properties, confirming Advax's utility as a general purpose vaccine adjuvant.