Poly(Lactide-co-Glycolide) Nanoparticle-Mediated Vaccine Delivery of Encapsulated Surface Antigen Protein of Hepatitis B Virus Elicits Effective Immune Response.

Abstract

Hepatitis B viral infection is one of the most important infectious diseases of the liver worldwide. Chronic infection with HBV often leads to cirrhosis and hepatocellular carcinoma. The currently licensed hepatitis B vaccine consists of recombinant hepatitis B surface antigen adsorbed into aluminum adjuvant and administered in three doses over the course of 6 months. However, this vaccine requires invasive administration and requires multiple booster doses. To avoid these limitations, nanoparticle (NP)-based vaccines lent itself as efficient adjuvants and delivery systems for the development of new generation vaccines. The biodegradable synthetic polymeric NPs poly(lactide-co-glycolide) (PLGA) was used in this study to formulate PLGA NPs encapsulated with hepatitis B surface protein to evaluate immune response in human peripheral blood lymphocytes in vitro. Formulation of HBP (HBV surface protein)-encapsulated PLGA (HB-nanovaccine [HB-NV]) was conducted by using double emulsion solvent evaporation technique (water-oil-water), which resulted in 94% encapsulation efficiency and 24% protein loading capacity. The resulted HB-NV had typical characteristics of spherical shape at an average size of 71.08 nm with higher densities and high stability dispersion of negatively charged NPs as assessed by atomic force microscopy, scanning electron microscopy, ultraviolet absorption spectrophotometry, zeta potential, and Fourier-transform infrared. The immune response to HB-NV was measured in vitro in lymphocytes, showed significant increase in levels of IL-2 and IFN-γ, as well as in CD4+ and CD8+ T cell counts, with a dose-dependent effect, examined by enzyme-linked immunosorbent assay and flow cytometry, respectively.