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.