Pegylation of DDA: TDB liposomal adjuvants reduces the vaccine depot effect and alters the Th1/Th2 immune responses

Randip Kaur, Vincent W. Bramwell, Daniel J. Kirby, Yvonne Perrie

Research output: Contribution to journalArticle

Abstract

The adjuvant efficacy of cationic liposomes composed of dimethyldioctadecylammonium bromide and trehalose dibehenate (DDA:TDB) is well established. Whilst the mechanism behind its immunostimulatory action is not fully understood, the ability of the formulation to promote a 'depot effect' is a consideration. The depot effect has been suggested to be primarily due to their cationic nature which results in electrostatic adsorption of the antigen and aggregation of the vesicles at the site of injection. The aim of the study was to further test this hypothesis by investigating whether sterically stabilising DDA:TDB with polyethylene glycol (PEG) reduces aggregation, and subsequently influences the formation of a depot at the site of injection. Results reported demonstrate that high (25%) levels of PEG was able to significantly inhibit the formation of a liposome depot and also severely limit the retention of antigen at the site, resulting in a faster drainage of the liposomes from the site of injection. This change in biodistribution profile was reflected in the immunisation response, where lower levels of IgG2b antibody and IFN-? and higher level of IL-5 cytokine were found. Furthermore entrapping antigen within DDA:TDB liposomes did not improve antigen retention at the injection site compared surface adsorbed antigen. © 2011 Elsevier B.V. All rights reserved.
LanguageEnglish
Pages72-77
Number of pages6
JournalJournal of Controlled Release
Volume158
Issue number1
Early online date17 Oct 2011
DOIs
Publication statusPublished - 28 Feb 2012

Fingerprint

Liposomes
Trehalose
Vaccines
Antigens
Injections
Interleukin-5
Surface Antigens
Static Electricity
Adsorption
Drainage
Immunization
Cytokines
bis(p-chlorophenyl)acetic acid
Antibodies
dimethyldioctadecylammonium

Keywords

  • DDA
  • polyethylene glycols
  • TDB
  • vaccine
  • adjuvant
  • depot effect

Cite this

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abstract = "The adjuvant efficacy of cationic liposomes composed of dimethyldioctadecylammonium bromide and trehalose dibehenate (DDA:TDB) is well established. Whilst the mechanism behind its immunostimulatory action is not fully understood, the ability of the formulation to promote a 'depot effect' is a consideration. The depot effect has been suggested to be primarily due to their cationic nature which results in electrostatic adsorption of the antigen and aggregation of the vesicles at the site of injection. The aim of the study was to further test this hypothesis by investigating whether sterically stabilising DDA:TDB with polyethylene glycol (PEG) reduces aggregation, and subsequently influences the formation of a depot at the site of injection. Results reported demonstrate that high (25{\%}) levels of PEG was able to significantly inhibit the formation of a liposome depot and also severely limit the retention of antigen at the site, resulting in a faster drainage of the liposomes from the site of injection. This change in biodistribution profile was reflected in the immunisation response, where lower levels of IgG2b antibody and IFN-? and higher level of IL-5 cytokine were found. Furthermore entrapping antigen within DDA:TDB liposomes did not improve antigen retention at the injection site compared surface adsorbed antigen. {\circledC} 2011 Elsevier B.V. All rights reserved.",
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Pegylation of DDA : TDB liposomal adjuvants reduces the vaccine depot effect and alters the Th1/Th2 immune responses. / Kaur, Randip; Bramwell, Vincent W.; Kirby, Daniel J.; Perrie, Yvonne.

In: Journal of Controlled Release, Vol. 158, No. 1, 28.02.2012, p. 72-77.

Research output: Contribution to journalArticle

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