Th1 immune responses can be modulated by varying dimethyldioctadecylammonium and distearoyl-sn-glycero-3-phosphocholine content in liposomal adjuvants
Hussain, Mohammed Jubair and Wilkinson, Alexander and Bramwell, Vincent W. and 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. ISSN 0022-3573 (https://doi.org/10.1111/jphp.12173)
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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.
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Item type: Article ID code: 56819 Dates: DateEvent31 March 2014Published17 February 2014Published Online10 October 2013AcceptedNotes: 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 https://dx.doi.org/10.1111/jphp.12173. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving Subjects: Medicine > Pharmacy and materia medica Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 01 Jul 2016 15:50 Last modified: 05 Oct 2024 00:24 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/56819