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

18 Citations (Scopus)
125 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)358-366
Number of pages9
JournalJournal of Pharmacy and Pharmacology
Volume66
Issue number3
Early online date17 Feb 2014
DOIs
Publication statusPublished - 31 Mar 2014

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

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