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Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines.

Abstract：

: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.

journal_name

Vaccine

journal_title

Vaccine

authors

Carstens MG,Camps MG,Henriksen-Lacey M,Franken K,Ottenhoff TH,Perrie Y,Bouwstra JA,Ossendorp F,Jiskoot W

doi

10.1016/j.vaccine.2011.04.081

subject

Has Abstract

pub_date

2011-06-24 00:00:00

pages

4761-70

issue

29-30

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(11)00636-0

journal_volume

29

pub_type

杂志文章

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