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纳米疫苗在抗原呈递细胞交叉呈递以激活CD8 T细胞应答中的作用

The Role of Nanovaccine in Cross-Presentation of Antigen-Presenting Cells for the Activation of CD8 T Cell Responses.

作者信息

Kim Cheol Gyun, Kye Yoon-Chul, Yun Cheol-Heui

机构信息

Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea.

Center for Food and Bioconvergence, Seoul National University, Seoul 08826, Korea.

出版信息

Pharmaceutics. 2019 Nov 15;11(11):612. doi: 10.3390/pharmaceutics11110612.

Abstract

Explosive growth in nanotechnology has merged with vaccine development in the battle against diseases caused by bacterial or viral infections and malignant tumors. Due to physicochemical characteristics including size, viscosity, density and electrostatic properties, nanomaterials have been applied to various vaccination strategies. Nanovaccines, as they are called, have been the subject of many studies, including review papers from a material science point of view, although a mode of action based on a biological and immunological understanding has yet to emerge. In this review, we discuss nanovaccines in terms of CD8 T cell responses, which are essential for antiviral and anticancer therapies. We focus mainly on the role and mechanism, with particular attention to the functional aspects, of nanovaccines in inducing cross-presentation, an unconventional type of antigen-presentation that activates CD8 T cells upon administration of exogenous antigens, in dendritic cells followed by activation of antigen-specific CD8 T cell responses. Two major intracellular mechanisms that nanovaccines harness for cross-presentation are described; one is endosomal swelling and rupture, and the other is membrane fusion. Both processes eventually allow exogenous vaccine antigens to be exported from phagosomes to the cytosol followed by loading on major histocompatibility complex class I, triggering clonal expansion of CD8 T cells. Advancement of nanotechnology with an enhanced understanding of how nanovaccines work will contribute to the design of more effective and safer nanovaccines.

摘要

纳米技术的迅猛发展已与疫苗研发相结合,用于对抗由细菌或病毒感染以及恶性肿瘤引起的疾病。由于纳米材料具有包括尺寸、粘度、密度和静电特性在内的物理化学特性,它们已被应用于各种疫苗接种策略。所谓的纳米疫苗已成为许多研究的主题,包括从材料科学角度撰写的综述论文,尽管基于生物学和免疫学理解的作用模式尚未出现。在本综述中,我们从CD8 T细胞反应的角度讨论纳米疫苗,这对抗病毒和抗癌治疗至关重要。我们主要关注纳米疫苗在诱导交叉呈递中的作用和机制,尤其关注其功能方面,交叉呈递是一种非常规的抗原呈递类型,在外源抗原给药后,可在树突状细胞中激活CD8 T细胞,随后激活抗原特异性CD8 T细胞反应。本文描述了纳米疫苗用于交叉呈递的两种主要细胞内机制;一种是内体肿胀和破裂,另一种是膜融合。这两个过程最终都能使外源疫苗抗原从吞噬体输出到细胞质中,随后加载到主要组织相容性复合体I类上,触发CD8 T细胞的克隆扩增。随着对纳米疫苗作用方式的深入理解,纳米技术的进步将有助于设计出更有效、更安全的纳米疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edc/6920862/c8bdf32e48fb/pharmaceutics-11-00612-g001.jpg

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