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.
| Language | English |
|---|---|
| Pages | 358-366 |
| Number of pages | 9 |
| Journal | Journal of Pharmacy and Pharmacology |
| Volume | 66 |
| Issue number | 3 |
| Early online date | 17 Feb 2014 |
| DOIs | |
| Publication status | Published - 31 Mar 2014 |
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Keywords
- immunologic adjuvants
- animals
- antigens
- cations
- female
- glycolipids
- cellular immunity
- liposomes
- mice
- mice, inbred C57BL
- phosphatidylcholines
- quaternary ammonium compounds
- Th1 cells
- vaccines
- cationic liposomes
- dimethyldioctadecylammonium
- distearoyl-sn-glycero-3-phosphocholine
- Th1 responses
- vaccine adjuvant
Cite this
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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 Jubair; Wilkinson, Alexander; Bramwell, Vincent W.; Christensen, Dennis; Perrie, Yvonne.
In: Journal of Pharmacy and Pharmacology, Vol. 66, No. 3, 31.03.2014, p. 358-366.Research output: Contribution to journal › Article
TY - JOUR
T1 - Th1 immune responses can be modulated by varying dimethyldioctadecylammonium and distearoyl-sn-glycero-3-phosphocholine content in liposomal adjuvants
AU - Hussain, Mohammed Jubair
AU - Wilkinson, Alexander
AU - Bramwell, Vincent W.
AU - Christensen, Dennis
AU - Perrie, Yvonne
N1 - 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
PY - 2014/3/31
Y1 - 2014/3/31
N2 - 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.
AB - 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.
KW - immunologic adjuvants
KW - animals
KW - antigens
KW - cations
KW - female
KW - glycolipids
KW - cellular immunity
KW - liposomes
KW - mice
KW - mice, inbred C57BL
KW - phosphatidylcholines
KW - quaternary ammonium compounds
KW - Th1 cells
KW - vaccines
KW - cationic liposomes
KW - dimethyldioctadecylammonium
KW - distearoyl-sn-glycero-3-phosphocholine
KW - Th1 responses
KW - vaccine adjuvant
UR - http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)2042-7158
U2 - 10.1111/jphp.12173
DO - 10.1111/jphp.12173
M3 - Article
VL - 66
SP - 358
EP - 366
JO - Journal of Pharmacy and Pharmacology
T2 - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
SN - 0022-3573
IS - 3
ER -