Open AccessT h1 immune responses can be modulated by varying dimethyldioctadecylammonium and distearoyl‐sn‐glycero‐3‐phosphocholine content in liposomal adjuvants
Author(s) -
Hussain Mohammed Jubair,
Wilkinson Alexander,
Bramwell Vincent W.,
Christensen Dennis,
Perrie Yvonne
Publication year - 2014
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.12173
Subject(s) - adjuvant , liposome , antigen , immune system , chemistry , cationic liposome , phosphocholine , vesicle , immunology , phosphatidylcholine , membrane , biology , biochemistry , genetic enhancement , phospholipid , gene
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‐ R v2660c, 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 H 56 antigen ( H ybrid56; Ag 85 B ‐ ESAT 6‐ Rv 2660c); 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.