A case-study investigating the physicochemical characteristics that dictate the function of a liposomal adjuvant

Yvonne Perrie, Elisabeth Kastner, Randip Kaur, Alexander Wilkinson, Andrew J. Ingham

Research output: Contribution to journalArticle

Abstract

A range of particulate delivery systems have been considered as vaccine adjuvants. Of these systems, liposomes offer a range of advantages including versatility and flexibility in design format and their ability to incorporate a range of immunomodulators and antigens. Here we briefly outline research, from within our laboratories, which focused on the systematic evaluation of cationic liposomes as vaccines adjuvants. Our aim was to identify physicochemical characteristics that correlate with vaccine efficacy, with particular consideration of the interlink between depot-forming action and immune responses. A variety of parameters were investigated and over a range of studies we have confirmed that cationic liposomes, based on dimethyldioctadecylammonium bromide and trehalose 6,6'-dibehenate formed a depot at the injection site, which stimulates recruitment of antigen presenting cells to the injection site and promotes strong humoral and cell-mediated immune responses. Physicochemical factors which promote a strong vaccine depot include the combination of a high cationic charge and electrostatic binding of the antigen to the liposome system and the use of lipids with high transition temperatures, which form rigid bilayer vesicles. Reduction in vesicle size of cationic vesicles did not promote enhanced drainage from the injection site. However, reducing the cationic nature through substitution of the cationic lipid for a neutral lipid, or by masking of the charge using PEGylation, resulted in a reduced depot formation and reduced Th1-type immune responses, while Th2-type responses were less influenced. These studies confirm that the physicochemical characteristics of particulate-based adjuvants play a key role in the modulation of immune responses.
LanguageEnglish
Pages1374-1381
Number of pages8
JournalHuman Vaccines and Immunotherapeutics
Volume9
Issue number6
Early online date12 Apr 2013
DOIs
Publication statusPublished - Jun 2013

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Liposomes
Vaccines
Lipids
Injections
Antigens
Transition Temperature
Immunologic Factors
Antigen-Presenting Cells
Static Electricity
Drainage
Research

Bibliographical note

This work was supported by NewTBVAC and made possible by the European Commission (contract no. LSHP-CT-2003-503367 and FP7-HEALTH-F3-2009-241745)

Cite this

Perrie, Yvonne ; Kastner, Elisabeth ; Kaur, Randip ; Wilkinson, Alexander ; Ingham, Andrew J. / A case-study investigating the physicochemical characteristics that dictate the function of a liposomal adjuvant. In: Human Vaccines and Immunotherapeutics. 2013 ; Vol. 9, No. 6. pp. 1374-1381.
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A case-study investigating the physicochemical characteristics that dictate the function of a liposomal adjuvant. / Perrie, Yvonne; Kastner, Elisabeth; Kaur, Randip; Wilkinson, Alexander; Ingham, Andrew J.

In: Human Vaccines and Immunotherapeutics, Vol. 9, No. 6, 06.2013, p. 1374-1381.

Research output: Contribution to journalArticle

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