Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines
Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines
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DOI：
10.1016/j.vaccine.2011.04.081
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发表时间：
2011-06-24
期刊：
影响因子：
5.5
通讯作者：
Jiskoot, Wim
中科院分区：
文献类型：
--
作者：
Carstens, Myrra G.;Camps, Marcel G. M.;Jiskoot, Wim
质粒DNA（pDNA）在阳离子脂质体中的配制是提高DNA疫苗效力的有希望的策略。在这方面，理化参数如脂质体大小可能对其功效很重要。本研究的目的是研究囊泡大小对小鼠皮下接种后脂质体pDNA疫苗的体内性能的影响。用双重放射性标记的pDNA-脂质体研究了由卵PC、DOPE和DOTAP组成的500 nm（PDI0.6）和140 nm（PDI0.15）两种大小的阳离子脂质体与编码OVA的pDNA的包封物的组织分布。在同源和异源接种时间表中以3周间隔施用后，研究了它们引发细胞和体液免疫应答的效力。结果表明，将pDNA包封到阳离子脂质体中导致在注射部位沉积，并且在大囊泡尺寸下观察到最强的保留。接种研究表明，与大的异分散脂质体或裸pDNA相比，用小的单分散pDNA-脂质体接种后，对OVA特异性功能性CD 8（+）T细胞的诱导更稳健，抗体水平更高。在小阳离子脂质体上引入PEG涂层导致增强的淋巴引流，但与非PEG化脂质体相比，免疫应答没有改善。总之，结果表明，脂质体的物理化学性质对其作为pDNA疫苗载体的性能至关重要，阳离子电荷和小尺寸是皮下DNA疫苗接种的有利性质。(C)2011爱思唯尔有限公司保留所有权利。
The formulation of plasmid DNA (pDNA) in cationic liposomes is a promising strategy to improve the potency of DNA vaccines. In this respect, physicochemical parameters such as liposome size may be important for their efficacy. The aim of the current study was to investigate the effect of vesicle size on the in vivo performance of liposomal pDNA vaccines after subcutaneous vaccination in mice. The tissue distribution of cationic liposomes of two sizes, 500 nm (PDI 0.6) and 140 nm (PDI 0.15), composed of egg PC, DOPE and DOTAP, with encapsulated OVA-encoding pDNA, was studied by using dual radiolabeled pDNA-liposomes. Their potency to elicit cellular and humoral immune responses was investigated upon application in a homologous and heterologous vaccination schedule with 3 week intervals. It was shown that encapsulation of pDNA into cationic lipsomes resulted in deposition at the site of injection, and strongest retention was observed at large vesicle size. The vaccination studies demonstrated a more robust induction of OVA-specific, functional CD8(+) T-cells and higher antibody levels upon vaccination with small monodisperse pDNA-liposomes, as compared to large heterodisperse liposomes or naked pDNA. The introduction of a PEG-coating on the small cationic liposomes resulted in enhanced lymphatic drainage, but immune responses were not improved when compared to non-PEGylated liposomes. In conclusion, it was shown that the physicochemical properties of the liposomes are of crucial importance for their performance as pDNA vaccine carrier, and cationic charge and small size are favorable properties for subcutaneous DNA vaccination. (C) 2011 Elsevier Ltd. All rights reserved.