Liposomes based on dimethyldioctadecylammonium promote a depot effect and enhance immunogenicity of soluble antigen

Malou Henriksen-Lacey, Vincent W. Bramwell, Dennis Christensen, Else Marie Agger, Peter Andersen, Yvonne Perrie

Research output: Contribution to journalArticle

Abstract

The mechanism behind the immunostimulatory effect obtained with the cationic liposomal vaccine adjuvant DDA:TDB remains unclear. One of the proposed hypotheses is the 'depot effect' in which the liposomal carrier helps to retain the antigen at the injection site thereby increasing the time of vaccine exposure to the immune cells. In the present study we devise a method to quantify the in vivo movement of liposomes and vaccine antigen using the radioisotopes H(3) and I(125) respectively. H(3)-labeled liposomes composed of dimethyldioctadecylammonium bromide (DDA) or an 8:1 molar ratio of DDA and trehalose 6,6-dibehenate (TDB) were administered in combination with I(125)-labeled Ag85B-ESAT-6 antigen, both via intramuscular and subcutaneous injection to mice. Furthermore characterisation of the liposomal system in simulated in vivo conditions was undertaken. Our results show that this dual-labeling technique is functional and reproducible. The administration of Ag85B-ESAT-6 without a liposomal carrier leads to rapid dissemination of the antigen from the site of injection. The administration of Ag85B-ESAT-6 together with either DDA or DDA:TDB liposomes however leads to deposition of the antigen at the injection site with detectable levels still being present 14 days post injection. Neither the incorporation of TDB nor the route of injection had any significant influence on the depot effect of DDA-based liposomes. The presence of TDB in DDA liposomes improves draining of liposomes to the lymph node in addition to increasing monocyte influx to the site of injection as highlighted by the intensive blue colouring of the injection site after pontamine blue staining of phagocytic cells in vivo. Our findings provide conclusive evidence for a cationic liposome-mediated deposition of antigen at the injection site with improved monocyte infiltration.
LanguageEnglish
Pages180-186
Number of pages7
JournalJournal of Controlled Release
Volume142
Issue number2
Early online date26 Oct 2009
DOIs
Publication statusPublished - 3 Mar 2010

Fingerprint

Liposomes
Trehalose
Antigens
Injections
Vaccines
Monocytes
dimethyldioctadecylammonium
Intramuscular Injections
Subcutaneous Injections
Phagocytes
Radioisotopes
Lymph Nodes
Staining and Labeling

Keywords

  • animals
  • bacterial antigens
  • bacterial proteins
  • bacterial vaccines
  • blood pProteins
  • glycolipids
  • liposomes
  • mice
  • inbred BALB C mice
  • quaternary ammonium compounds

Cite this

Henriksen-Lacey, Malou ; Bramwell, Vincent W. ; Christensen, Dennis ; Agger, Else Marie ; Andersen, Peter ; Perrie, Yvonne. / Liposomes based on dimethyldioctadecylammonium promote a depot effect and enhance immunogenicity of soluble antigen. In: Journal of Controlled Release. 2010 ; Vol. 142, No. 2. pp. 180-186.
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abstract = "The mechanism behind the immunostimulatory effect obtained with the cationic liposomal vaccine adjuvant DDA:TDB remains unclear. One of the proposed hypotheses is the 'depot effect' in which the liposomal carrier helps to retain the antigen at the injection site thereby increasing the time of vaccine exposure to the immune cells. In the present study we devise a method to quantify the in vivo movement of liposomes and vaccine antigen using the radioisotopes H(3) and I(125) respectively. H(3)-labeled liposomes composed of dimethyldioctadecylammonium bromide (DDA) or an 8:1 molar ratio of DDA and trehalose 6,6-dibehenate (TDB) were administered in combination with I(125)-labeled Ag85B-ESAT-6 antigen, both via intramuscular and subcutaneous injection to mice. Furthermore characterisation of the liposomal system in simulated in vivo conditions was undertaken. Our results show that this dual-labeling technique is functional and reproducible. The administration of Ag85B-ESAT-6 without a liposomal carrier leads to rapid dissemination of the antigen from the site of injection. The administration of Ag85B-ESAT-6 together with either DDA or DDA:TDB liposomes however leads to deposition of the antigen at the injection site with detectable levels still being present 14 days post injection. Neither the incorporation of TDB nor the route of injection had any significant influence on the depot effect of DDA-based liposomes. The presence of TDB in DDA liposomes improves draining of liposomes to the lymph node in addition to increasing monocyte influx to the site of injection as highlighted by the intensive blue colouring of the injection site after pontamine blue staining of phagocytic cells in vivo. Our findings provide conclusive evidence for a cationic liposome-mediated deposition of antigen at the injection site with improved monocyte infiltration.",
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Henriksen-Lacey, M, Bramwell, VW, Christensen, D, Agger, EM, Andersen, P & Perrie, Y 2010, 'Liposomes based on dimethyldioctadecylammonium promote a depot effect and enhance immunogenicity of soluble antigen' Journal of Controlled Release, vol. 142, no. 2, pp. 180-186. https://doi.org/10.1016/j.jconrel.2009.10.022

Liposomes based on dimethyldioctadecylammonium promote a depot effect and enhance immunogenicity of soluble antigen. / Henriksen-Lacey, Malou; Bramwell, Vincent W.; Christensen, Dennis; Agger, Else Marie; Andersen, Peter; Perrie, Yvonne.

In: Journal of Controlled Release, Vol. 142, No. 2, 03.03.2010, p. 180-186.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Liposomes based on dimethyldioctadecylammonium promote a depot effect and enhance immunogenicity of soluble antigen

AU - Henriksen-Lacey, Malou

AU - Bramwell, Vincent W.

AU - Christensen, Dennis

AU - Agger, Else Marie

AU - Andersen, Peter

AU - Perrie, Yvonne

N1 - Copyright 2009 Elsevier B.V. All rights reserved.

PY - 2010/3/3

Y1 - 2010/3/3

N2 - The mechanism behind the immunostimulatory effect obtained with the cationic liposomal vaccine adjuvant DDA:TDB remains unclear. One of the proposed hypotheses is the 'depot effect' in which the liposomal carrier helps to retain the antigen at the injection site thereby increasing the time of vaccine exposure to the immune cells. In the present study we devise a method to quantify the in vivo movement of liposomes and vaccine antigen using the radioisotopes H(3) and I(125) respectively. H(3)-labeled liposomes composed of dimethyldioctadecylammonium bromide (DDA) or an 8:1 molar ratio of DDA and trehalose 6,6-dibehenate (TDB) were administered in combination with I(125)-labeled Ag85B-ESAT-6 antigen, both via intramuscular and subcutaneous injection to mice. Furthermore characterisation of the liposomal system in simulated in vivo conditions was undertaken. Our results show that this dual-labeling technique is functional and reproducible. The administration of Ag85B-ESAT-6 without a liposomal carrier leads to rapid dissemination of the antigen from the site of injection. The administration of Ag85B-ESAT-6 together with either DDA or DDA:TDB liposomes however leads to deposition of the antigen at the injection site with detectable levels still being present 14 days post injection. Neither the incorporation of TDB nor the route of injection had any significant influence on the depot effect of DDA-based liposomes. The presence of TDB in DDA liposomes improves draining of liposomes to the lymph node in addition to increasing monocyte influx to the site of injection as highlighted by the intensive blue colouring of the injection site after pontamine blue staining of phagocytic cells in vivo. Our findings provide conclusive evidence for a cationic liposome-mediated deposition of antigen at the injection site with improved monocyte infiltration.

AB - The mechanism behind the immunostimulatory effect obtained with the cationic liposomal vaccine adjuvant DDA:TDB remains unclear. One of the proposed hypotheses is the 'depot effect' in which the liposomal carrier helps to retain the antigen at the injection site thereby increasing the time of vaccine exposure to the immune cells. In the present study we devise a method to quantify the in vivo movement of liposomes and vaccine antigen using the radioisotopes H(3) and I(125) respectively. H(3)-labeled liposomes composed of dimethyldioctadecylammonium bromide (DDA) or an 8:1 molar ratio of DDA and trehalose 6,6-dibehenate (TDB) were administered in combination with I(125)-labeled Ag85B-ESAT-6 antigen, both via intramuscular and subcutaneous injection to mice. Furthermore characterisation of the liposomal system in simulated in vivo conditions was undertaken. Our results show that this dual-labeling technique is functional and reproducible. The administration of Ag85B-ESAT-6 without a liposomal carrier leads to rapid dissemination of the antigen from the site of injection. The administration of Ag85B-ESAT-6 together with either DDA or DDA:TDB liposomes however leads to deposition of the antigen at the injection site with detectable levels still being present 14 days post injection. Neither the incorporation of TDB nor the route of injection had any significant influence on the depot effect of DDA-based liposomes. The presence of TDB in DDA liposomes improves draining of liposomes to the lymph node in addition to increasing monocyte influx to the site of injection as highlighted by the intensive blue colouring of the injection site after pontamine blue staining of phagocytic cells in vivo. Our findings provide conclusive evidence for a cationic liposome-mediated deposition of antigen at the injection site with improved monocyte infiltration.

KW - animals

KW - bacterial antigens

KW - bacterial proteins

KW - bacterial vaccines

KW - blood pProteins

KW - glycolipids

KW - liposomes

KW - mice

KW - inbred BALB C mice

KW - quaternary ammonium compounds

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DO - 10.1016/j.jconrel.2009.10.022

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