Formulation and Evaluation of a Novel Needle-Free Hepatitis B Surface Antigen Delivery System

Problem statement: Hepatitis B is a major public health problem, killing 1-2 million people annually, despite the introduction of an effective vaccine in 1982. Approximately 400 million persons worldwide have chronic hepatitis B. This is due to problems associated with vaccine delivery, stability and cost. Hence the present challenge in Vaccinology is to develop safer, cheaper and easy-to-deliver forms of vaccines. A novel needle-free oral vaccine will be an ideal tool to fight with this silent killer disease. Approach: Hence a study was conducted with the aim of formulating and evaluating an effective oral HBsAg vaccine. HBsAg-loaded microspheres were prepared by microencapsulation using albumin as polymer and sodium taurocholate as permeation enhancer. Bacitracin and aprotinin were incorporated as protease inhibitors. After in vitro studies, optimized drug-loaded microspheres were encapsulated in hard gelatin capsules which were further enteric coated with cellulose acetate phthalate. In vivo experiments were conducted in rabbits. Control group was administered with 20 µg of HBsAg intramuscularly and the test groups were given different formulations of oral vaccine as per the current vaccination schedule of 0, 1 and 6 months. Immunogenicity was compared with IM injected vaccine control group. Results: HBsAg microspheres with albumin as polymer and bacitracin as protease inhibitor induced immune response with specific antibodies and cell mediated immunity better than the formulation with aprotinin as protease inhibitor (p = 0.047). Vaccine-related adverse events were absent in all immunized rabbits. Basic haematological, biochemical and physical parameters were within normal limits. Conclusion: The stability exhibited by this vaccine at room temperature can be extremely useful to overcome the incomplete vaccine coverage due to cold chain requirement. Impressive large logistical advantages and elimination of blood-borne infections are other major benefits, which may have a great impact on global HBsAg immunization acceptance and compliance and on hepatitis B disease burden.