title: Th1 immune responses can be modulated by varying dimethyldioctadecylammonium and distearoyl-sn-glycero-3-phosphocholine content in liposomal adjuvants.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These results suggest Th1 responses can be controlled by tailoring the DDA/DSPC ratio within the liposomal adjuvant system.
authors.affiliation: School of Life and Health Sciences, Aston University, Birmingham, UK.
authors.forename: Mohammed Jubair
authors.initials: MJ
authors.lastname: Hussain
authors.forename: Alexander
authors.initials: A
authors.lastname: Wilkinson
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Bramwell
authors.forename: Dennis
authors.initials: D
authors.lastname: Christensen
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Perrie
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000737:chemistry; D002412:Cations; D005260:Female; D006017:Glycolipids / Q000008:administration & dosage / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects*; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010713:Phosphatidylcholines / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D018417:Th1 Cells; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D002412:Cations; D006017:Glycolipids; D008081:Liposomes; D010713:Phosphatidylcholines; D000644:Quaternary Ammonium Compounds; D014612:Vaccines; C507803:trehalose 6,6'-dibehenate; C015831:dimethyldioctadecylammonium; C010942:1,2-distearoyllecithin
keywords: Th1 responses; cationic liposomes; dimethyldioctadecylammonium; distearoyl-sn-glycero-3-phosphocholine; vaccine adjuvant