Enhanced immunogenicity of a hepatitis B virus peptide vaccine using oligosaccharide ester derivative microparticles

Controlled release microspheres can overcome many of the disadvantages of multiple vaccine delivery such as rate of uptake and cost of administration. Proteins and peptides are difficult to administer using conventional polymers owing to protein degradation, premature release and stability. Here we report the successful development of room temperature stable, controlled release formulations using oligosaccharide ester derivatives (OEDs) of trehalose and a synthetic peptide analogue of hepatitis B surface antigen. Employing a range of different OED preparations, we have optimised the immunogenicity of the peptide formulation such that mice injected with a single preparation of microspheres consisting of trehalose octaacetate (TR101; Group G) produce high titre anti-hepatitis B (anti-HBs) surface antigen antibodies. The kinetics of the immune response could be manipulated with different peptide/OED formulations and correlated with the OED composition of the microspheres. Our data demonstrate the considerable potential of OED microspheres as novel delivery systems for vaccines. The ability to induce strong immune responses, without the requirement for multiple doses or cold-chain storage, could radically improve vaccination programmes in developing countries.