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

Myrra G. Carstens, Marcel G. M. Camps, Malou Henriksen-Lacey, Kees Franken, Tom H.M. Ottenhoff, Yvonne Perrie, Joke A. Bouwstra, Ferry Ossendorp, Wim Jiskoot

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

LanguageEnglish
Pages4761-4770
Number of pages10
JournalVaccine
Volume29
Issue number29-30
DOIs
Publication statusPublished - 24 Jun 2011

Fingerprint

DNA Vaccines
recombinant vaccines
Liposomes
plasmids
immune response
Plasmids
vaccination
Vaccination
DNA
Vaccine Potency
tissues
injection site
tissue distribution
encapsulation
humoral immunity
cell-mediated immunity
Tissue Distribution
Humoral Immunity
coatings
Cellular Immunity

Keywords

  • DNA vaccines
  • cationic liposomes
  • biodistribution
  • vaccine carrier

Cite this

Carstens, M. G., Camps, M. G. M., Henriksen-Lacey, M., Franken, K., Ottenhoff, T. H. M., Perrie, Y., ... Jiskoot, W. (2011). Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines. Vaccine, 29(29-30), 4761-4770. https://doi.org/10.1016/j.vaccine.2011.04.081
Carstens, Myrra G. ; Camps, Marcel G. M. ; Henriksen-Lacey, Malou ; Franken, Kees ; Ottenhoff, Tom H.M. ; Perrie, Yvonne ; Bouwstra, Joke A. ; Ossendorp, Ferry ; Jiskoot, Wim. / Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines. In: Vaccine. 2011 ; Vol. 29, No. 29-30. pp. 4761-4770.
@article{c6ea65763ac34b04b8d06db249c082ee,
title = "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.",
keywords = "DNA vaccines, cationic liposomes, biodistribution, vaccine carrier",
author = "Carstens, {Myrra G.} and Camps, {Marcel G. M.} and Malou Henriksen-Lacey and Kees Franken and Ottenhoff, {Tom H.M.} and Yvonne Perrie and Bouwstra, {Joke A.} and Ferry Ossendorp and Wim Jiskoot",
note = "Copyright {\circledC} 2011 Elsevier Ltd. All rights reserved.",
year = "2011",
month = "6",
day = "24",
doi = "10.1016/j.vaccine.2011.04.081",
language = "English",
volume = "29",
pages = "4761--4770",
journal = "Vaccine",
issn = "0264-410X",
number = "29-30",

}

Carstens, MG, Camps, MGM, Henriksen-Lacey, M, Franken, K, Ottenhoff, THM, Perrie, Y, Bouwstra, JA, Ossendorp, F & Jiskoot, W 2011, 'Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines' Vaccine, vol. 29, no. 29-30, pp. 4761-4770. https://doi.org/10.1016/j.vaccine.2011.04.081

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; Jiskoot, Wim.

In: Vaccine, Vol. 29, No. 29-30, 24.06.2011, p. 4761-4770.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines

AU - Carstens, Myrra G.

AU - Camps, Marcel G. M.

AU - Henriksen-Lacey, Malou

AU - Franken, Kees

AU - Ottenhoff, Tom H.M.

AU - Perrie, Yvonne

AU - Bouwstra, Joke A.

AU - Ossendorp, Ferry

AU - Jiskoot, Wim

N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.

PY - 2011/6/24

Y1 - 2011/6/24

N2 - 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.

AB - 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.

KW - DNA vaccines

KW - cationic liposomes

KW - biodistribution

KW - vaccine carrier

U2 - 10.1016/j.vaccine.2011.04.081

DO - 10.1016/j.vaccine.2011.04.081

M3 - Article

VL - 29

SP - 4761

EP - 4770

JO - Vaccine

T2 - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 29-30

ER -

Carstens MG, Camps MGM, Henriksen-Lacey M, Franken K, Ottenhoff THM, Perrie Y et al. Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines. Vaccine. 2011 Jun 24;29(29-30):4761-4770. https://doi.org/10.1016/j.vaccine.2011.04.081