Th1 immune responses can be modulated by varying dimethyldioctadecylammonium and distearoyl-sn-glycero-3-phosphocholine content in liposomal adjuvants

Mohammed J. Hussain, Alexander Wilkinson, Vincent W. Bramwell, Dennis Christensen, Yvonne Perrie

Research output: Contribution to journalArticle

Abstract

Objectives Cationic liposomes of dimethyldioctadecylammonium bromide (DDA) combined with trehalose 6,6′-dibehenate (TDB) elicit strong cell-mediated and antibody immune responses; DDA facilitates antigen adsorption and presentation while TDB potentiates the immune response. To further investigate the role of DDA, DDA was replaced with the neutral lipid of distearoyl-sn- glycero-3-phosphocholine (DSPC) over a series of concentrations and these systems investigated as adjuvants for the delivery of Ag85B-ESAT-6-Rv2660c, a multistage tuberculosis vaccine. Methods Liposomal were prepared at a 5: 1 DDA-TDB weight ratio and DDA content incrementally replaced with DSPC. The physicochemical characteristics were assessed (vesicle size, zeta potential and antigen loading), and the ability of these systems to act as adjuvants was considered. Key findings As DDA was replaced with DSPC within the liposomal formulation, the cationic nature of the vesicles decreases as does electrostatically binding of the anionic H56 antigen (Hybrid56; Ag85B-ESAT6-Rv2660c); however, only when DDA was completed replaced with DSPC did vesicle size increase significantly. T-helper 1 (Th1)-type cell-mediated immune responses reduced. This reduction in responses was attributed to the replacement of DDA with DSPC rather than the reduction in DDA dose concentration within the formulation. Conclusion These results suggest Th1 responses can be controlled by tailoring the DDA/DSPC ratio within the liposomal adjuvant system. © 2013 Royal Pharmaceutical Society.
Original languageEnglish
Pages (from-to)358-366
Number of pages9
JournalJournal of Pharmacy and Pharmacology
Volume66
Issue number3
Early online date19 Nov 2013
DOIs
Publication statusPublished - Mar 2014

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Phosphorylcholine
Trehalose
dimethyldioctadecylammonium
Pharmaceutical Societies
Tuberculosis Vaccines
Antigens
Th1 Cells
Antigen Presentation
Liposomes
Adsorption
Antibody Formation
Lipids

Bibliographical note

This is the peer reviewed version of the following article: Hussain, M. J., Wilkinson, A., Bramwell, V. W., Christensen, D., & Perrie, Y. (2014). Th1 immune responses can be modulated by varying dimethyldioctadecylammonium and distearoyl-sn-glycero-3-phosphocholine content in liposomal adjuvants. Journal of pharmacy and pharmacology, 66(3), 358-366., which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/jphp.12173

This work was partly funded by newTBVAC (contract no. Health-F3-2009-241745). NewTBVAC has been made possible by contributions from the European Commission.

Keywords

  • cationic liposomes
  • dimethyldioctadecylammonium
  • distearoyl-sn-glycero-3-phosphocholine
  • Th1 responses
  • vaccine adjuvant

Cite this

Hussain, Mohammed J. ; Wilkinson, Alexander ; Bramwell, Vincent W. ; Christensen, Dennis ; Perrie, Yvonne. / Th1 immune responses can be modulated by varying dimethyldioctadecylammonium and distearoyl-sn-glycero-3-phosphocholine content in liposomal adjuvants. In: Journal of Pharmacy and Pharmacology. 2014 ; Vol. 66, No. 3. pp. 358-366.
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abstract = "Objectives Cationic liposomes of dimethyldioctadecylammonium bromide (DDA) combined with trehalose 6,6′-dibehenate (TDB) elicit strong cell-mediated and antibody immune responses; DDA facilitates antigen adsorption and presentation while TDB potentiates the immune response. To further investigate the role of DDA, DDA was replaced with the neutral lipid of distearoyl-sn- glycero-3-phosphocholine (DSPC) over a series of concentrations and these systems investigated as adjuvants for the delivery of Ag85B-ESAT-6-Rv2660c, a multistage tuberculosis vaccine. Methods Liposomal were prepared at a 5: 1 DDA-TDB weight ratio and DDA content incrementally replaced with DSPC. The physicochemical characteristics were assessed (vesicle size, zeta potential and antigen loading), and the ability of these systems to act as adjuvants was considered. Key findings As DDA was replaced with DSPC within the liposomal formulation, the cationic nature of the vesicles decreases as does electrostatically binding of the anionic H56 antigen (Hybrid56; Ag85B-ESAT6-Rv2660c); however, only when DDA was completed replaced with DSPC did vesicle size increase significantly. T-helper 1 (Th1)-type cell-mediated immune responses reduced. This reduction in responses was attributed to the replacement of DDA with DSPC rather than the reduction in DDA dose concentration within the formulation. Conclusion These results suggest Th1 responses can be controlled by tailoring the DDA/DSPC ratio within the liposomal adjuvant system. {\circledC} 2013 Royal Pharmaceutical Society.",
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Th1 immune responses can be modulated by varying dimethyldioctadecylammonium and distearoyl-sn-glycero-3-phosphocholine content in liposomal adjuvants. / Hussain, Mohammed J.; Wilkinson, Alexander; Bramwell, Vincent W.; Christensen, Dennis; Perrie, Yvonne.

In: Journal of Pharmacy and Pharmacology, Vol. 66, No. 3, 03.2014, p. 358-366.

Research output: Contribution to journalArticle

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