Fc receptor-targeting of immunogen as a strategy for enhanced antigen loading, vaccination, and protection using intranasally administered antigen-pulsed dendritic cells
Fc receptor-targeting of immunogen as a strategy for enhanced antigen loading, vaccination, and protection using intranasally administered antigen-pulsed dendritic cells
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DOI：
10.1016/j.vaccine.2014.07.050
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发表时间：
2014-09-08
期刊：
影响因子：
5.5
通讯作者：
Gosselin, Edmund J.
中科院分区：
文献类型：
--
作者：
Pham, Giang H.;Iglesias, Bibiana V.;Gosselin, Edmund J.
树突状细胞 (DC) 通过有效捕获、处理抗原 (Ag) 并将其呈递给初始 T 细胞，在适应性免疫的产生中发挥着关键作用。施用Ag脉冲DC也是增强对肿瘤和传染病生物体的免疫力的有效策略。研究还表明，将 Ag 靶向 Ag 呈递细胞上的 Fey 受体 (Fc gamma R) 可以增强体外和体内的体液和细胞免疫。具体来说，我们使用土拉弗朗西斯菌 (Ft) 传染病疫苗模型的研究表明，通过鼻内 (i.n.) 施用单克隆抗体 (mAb) 灭活的 Ft (iFt) 免疫复合物 (IC) 将免疫原靶向 Fc gamma R，可增强针对 Ft 攻击的保护。 Ft 是兔热病的病原体，兔热病是一种使人类和其他哺乳动物衰弱的疾病，也是一种 A 类生物威胁因子，尚无批准的疫苗。因此，使用 iFt Ag 作为模型免疫原，我们试图确定 iFt 体外靶向 DC 上的 Fc gamma R 是否会增强 i.n 的效力。施用 iFt 脉冲 DC。在这项研究中，使用 iFt 或 mAb-iFt IC 对骨髓来源的 DC (BMDC) 进行离体脉冲。鼻内施用 mAb-iFt 脉冲的 BMDC 增强了体液和细胞免疫反应，以及针对 Ft 活疫苗株 (LVS) 攻击的保护作用。由于 Fc gamma R 靶向，保护作用的增强与 BMDC 表面 iFt 负载的增加相关。然而，抑制性 Fc gamma RIIB 对这种增强没有影响。总之，将 Ag 离体靶向 DC 上的 Fc gamma R 提供了一种增强 DC 离体 Ag 负载的方法，从而减少所需的 Ag 量，同时还避免了 Fc gamma RIIB 的抑制影响。因此，这代表了一种简单且侵入性较小的策略，可提高离体脉冲 DC 疫苗对抗慢性传染病和癌症的效力。 (C) 2014 Elsevier Ltd. 保留所有权利。
Dendritic cells (DCs) play a critical role in the generation of adaptive immunity via the efficient capture, processing, and presentation of antigen (Ag) to naive T cells. Administration of Ag-pulsed DCs is also an effective strategy for enhancing immunity to tumors and infectious disease organisms. Studies have also demonstrated that targeting Ags to Fey receptors (Fc gamma R) on Ag presenting cells can enhance humoral and cellular immunity in vitro and in vivo. Specifically, our studies using a Francisella tularensis (Ft) infectious disease vaccine model have demonstrated that targeting immunogens to Fc gamma R via intranasal (i.n.) administration of monoclonal antibody (mAb)-inactivated Ft (iFt) immune complexes (ICs) enhances protection against Ft challenge. Ft is the causative agent of tularemia, a debilitating disease of humans and other mammals and a category A biothreat agent for which there is no approved vaccine. Therefore, using iFt Ag as a model immunogen, we sought to determine if ex vivo targeting of iFt to Fc gamma R on DCs would enhance the potency of i.n. administered iFt-pulsed DCs. In this study, bone marrow-derived DCs (BMDCs) were pulsed ex vivo with iFt or mAb-iFt ICs. Intranasal administration of mAb-iFt-pulsed BMDCs enhanced humoral and cellular immune responses, as well as protection against Ft live vaccine strain (LVS) challenge. Increased protection correlated with increased iFt loading on the BMDC surface as a consequence of Fc gamma R-targeting. However, the inhibitory Fc gamma RIIB had no impact on this enhancement. In conclusion, targeting Ag ex vivo to Fc gamma R on DCs provides a method for enhanced Ag loading of DCs ex vivo, thereby reducing the amount of Ag required, while also avoiding the inhibitory impact of Fc gamma RIIB. Thus, this represents a simple and less invasive strategy for increasing the potency of ex vivo-pulsed DC vaccines against chronic infectious diseases and cancer. (C) 2014 Elsevier Ltd. All rights reserved.