Hepatitis B vaccination typically requires a multi-dose administration protocol over a course of 3-6 months. Aiming at developing a single-shot formulation for hepatitis B vaccine (hepatitis B surface antigen (HBsAg)), a novel vaccine delivery system, the composite microspheres of alginate-chitosan-poly(lactic-co-glycolic acid) (PLGA), was synthesized by a two-step preparation. The composite microspheres showed distinct advantages over the conventional PLGA microspheres in aspects of the high loading capacity and the elimination of lyophilizing process. The loading capacity of the composite microspheres was about seven times higher than those in the conventional PLGA microspheres, due to the protein-friendly microenvironment created by the hydrophilic alginate-chitosan cores of the composite microspheres. This vaccine delivery system was shown to be able to induce robust immune responses by single injection and display no significant difference in HBsAg-specific antibody levels compared to the double-injection method.
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