Enhancement of immune response of HBsAg loaded poly(L-lactic acid) microspheres against Hepatitis B through incorporation of alum and chitosan

Purpose: Poly (L-lactic acid) (PLA) microparticles encapsulating Hepatitis B surface antigen (HBsAg) with alum and chitosan were investigated for their potential as a vaccine delivery system. Methods: The microparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method with polyvinyl alcohol (PVA) or chitosan as the external phase stabilising agent showed a significant increase in the encapsulation efficiency of the antigen. Results: PLA-Alum and PLA-chitosan microparticles induced HBsAg serum specific IgG antibody responses significantly higher than PLA only microparticles and free antigen following subcutaneous administration. Chitosan not only imparted a positive charge to the surface of the microparticles but was also able to increase the serum specific IgG antibody responses significantly. Conclusions: The cytokine assays showed that the serum IgG antibody response induced is different according to the formulation, indicated by the differential levels of interleukin 4 (IL-4), interleukin 6 (IL-6) and interferon gamma (IFN-γ). The microparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-4, IL-6 and IFN-γ

Plant-made vaccines in support of the Millennium Development Goals

Vaccines are one of the most successful public health achievements of the last century. Systematic immunisation programs have reduced the burden of infectious diseases on a global scale. However, there are limitations to the current technology, which often requires costly infrastructure and long lead times for production. Furthermore, the requirement to keep vaccines within the cold-chain throughout manufacture, transport and storage is often impractical and prohibitively expensive in developing countries—the very regions where vaccines are most needed. In contrast, plant-made vaccines (PMVs) can be produced at a lower cost using basic greenhouse agricultural methods, and do not need to be kept within such narrow temperature ranges. This increases the feasibility of developing countries producing vaccines locally at a small-scale to target the specific needs of the region. Additionally, the ability of plant-production technologies to rapidly produce large quantities of strain-specific vaccine demonstrates their potential use in combating pandemics. PMVs are a proven technology that has the potential to play an important role in increasing global health, both in the context of the 2015 Millennium Development Goals and beyond

Alginate–Chitosan–PLGA Composite Microspheres Enabling Single-Shot Hepatitis B Vaccination

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

Oral Vaccine Delivery: The Coming Age of Particulate Vaccines to Elicit Mucosal Immunity

With the evolution of different challenging diseases, there is an urgent need of vaccine development against them to save millions of lives around the world. Particlulate delivery system plays an important role by acting as self-adjuvant in form of particles and thus assisting the immunogenicity of vaccines. Particulate vaccines have shown to have improved uptake by antigen presenting cells as compared to the soluble antigen. Traditional injectable vaccines are generally poor inducers of mucosal immunity and are therefore less effective against infections at the mucosal site. Mucosal vaccines have been reported to provide additional secretory antibody mediated protection at the mucosal site of entry of the pathogen. In this chapter, we discuss the benefits of particulate drug delivery systems for oral delivery, the role of immune system in the gut, and a case study ofa novel particulate vaccine formulated into oral dissolving film for immunization via the buccal route. Key formulation components, process parameters and their biophysical characterizations have been discussed as well