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

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

LanguageEnglish
Pages358-366
Number of pages9
JournalJournal of Pharmacy and Pharmacology
Volume66
Issue number3
Early online date17 Feb 2014
DOIs
Publication statusPublished - 31 Mar 2014

Fingerprint

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

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

Hussain, Mohammed Jubair ; 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.",
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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 journalArticle

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

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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

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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 -