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

Carstens, Myrra G; Camps, Marcel G M; Henriksen-Lacey, Malou; Franken, Kees; Ottenhoff, Tom H M; Perrie, Yvonne; Bouwstra, Joke A; Ossendorp, Ferry and Jiskoot, Wim (2011). Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines. Vaccine, 29 (29-30), pp. 4761-70.

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.

Publication DOI: https://doi.org/10.1016/j.vaccine.2011.04.081
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences
Life & Health Sciences > Applied Health Research Group
Life & Health Sciences > Health Sciences
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Additional Information: Copyright © 2011 Elsevier Ltd. All rights reserved.
Uncontrolled Keywords: Animals,Antibodies,Biological Availability,CD8-Positive T-Lymphocytes,Drug Carriers,Female,Injections, Subcutaneous,Liposomes,Mice,Mice, Inbred BALB C,Mice, Inbred C57BL,Ovalbumin,Vaccination,Vaccines, DNA,Vaccines, Synthetic,Immunology and Microbiology(all),Infectious Diseases,Public Health, Environmental and Occupational Health,veterinary(all),Molecular Medicine
Published Date: 2011-06-24

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