title: Comparison of vesicle based antigen delivery systems for delivery of hepatitis B surface antigen.
abstract: There is a clinical need for a more effective vaccine against hepatitis B, and in particular vaccines that may be suitable for therapeutic administration. This study assesses the potential of cationic surfactant vesicle based formulations using two agents; the cationic amine containing [N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) or dimethyl dioctadecylammonium bromide (DDA) with hepatitis B surface antigen (HBsAg). Synthetic mycobacterial cord factor, trehalose 6,6'-dibehenate (TDB) has been used as an adjuvant and the addition of 1-monopalmitoyl glycerol (C16:0) (MP) and cholesterol (Chol) to DDA-TDB is assessed for its potential to facilitate formation of dehydration-rehydration vesicles (DRV) at room temperature, and the effect of this on immune responses. A DRV formulation is directly compared to an adsorbed formulation of the same composition and preparation protocol (MP:dioleoyl phosphoethanolamine (DOPE):Chol:DC-Chol) and the direct substitution of MP with phosphatidylcholine (PC) is also compared in DRV antigen-entrapped formulations. MP and Chol were shown to facilitate the use of DDA-TDB in DRV formulations prepared at room temperature, whilst there was marginal alteration of immunogenicity (a reduction in HBsAg-specific IL-2). The HBsAg adsorbed DRV formulation was not significantly different from the HBsAg entrapped DRV formulation. Overall, DDA formulations incorporating TDB showed markedly increased antigen specific splenocyte proliferation and elicited cytokine production concomitant with a strong T cell driven response, delineating formulations that may be useful for further evaluation of their clinical potential.
authors.affiliation: Medicines Research Unit, School of Life and Health Sciences, Aston University, Birmingham, UK.
authors.forename: Anil
authors.initials: A
authors.lastname: Vangala
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Bramwell
authors.forename: Sarah
authors.initials: S
authors.lastname: McNeil
authors.forename: Dennis
authors.initials: D
authors.lastname: Christensen
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Agger
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Perrie
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage* / Q000276:immunology; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000187:drug effects / Q000276:immunology
chemical_list: D006514:Hepatitis B Surface Antigens; D008081:Liposomes