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 and Perrie, Yvonne (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), pp. 358-366.

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.

Publication DOI: https://doi.org/10.1111/jphp.12173
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences
Life & Health Sciences > Chronic and Communicable Conditions
Additional Information: 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.
Uncontrolled Keywords: cationic liposomes,dimethyldioctadecylammonium,distearoyl-sn-glycero-3-phosphocholine,Th1 responses,vaccine adjuvant
Full Text Link: http://onlineli ... .12173/abstract
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2014-03
Authors: Hussain, Mohammed J.
Wilkinson, Alexander
Bramwell, Vincent W.
Christensen, Dennis
Perrie, Yvonne

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