Chitosan-based nanoparticles for improving immunization against hepatitis B infection

• Published in: Vaccine Vol. 28; no. 14; pp. 2607 - 2614
• Main Authors: Prego, Cecilia, Paolicelli, Patrizia, Díaz, Belen, Vicente, Sara, Sánchez, Alejandro, González-Fernández, África, Alonso, María José
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 19.03.2010; Elsevier; Elsevier Limited
• Subjects: Adjuvant; Adjuvants; Adjuvants, Immunologic - administration & dosage; Allergy and Immunology; Animals; Antigens; Applied microbiology; Biological and medical sciences; Chitosan - administration & dosage; Chitosan-based nanoparticles; Delayed-Action Preparations - administration & dosage; Drug Carriers - administration & dosage; Female; Freeze drying; Fundamental and applied biological sciences. Psychology; Hepatitis; Hepatitis B; Hepatitis B Antibodies - blood; Hepatitis B Surface Antigens - genetics; Hepatitis B Surface Antigens - immunology; Hepatitis B Vaccines - immunology; Human viral diseases; Immune system; Immunization; Immunization - methods; Immunoglobulin G - blood; Infectious diseases; Injections, Intramuscular; Medical sciences; Mice; Mice, Inbred BALB C; Microbiology; Molecular weight; Nanoparticles - administration & dosage; Subunit antigens; Tetanus; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Viral diseases; Viral hepatitis; Waste disposal; Subunit antigens; Adjuvant; Chitosan-based nanoparticles; Immunization; Nanoparticle; Hepatic disease; Polymer; Vaccine; Subunit; Infection; Antigen; Viral hepatitis B; Viral disease; Immunological adjuvant; Digestive diseases; Chitosan
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.01.011

Abstract The design of effective vaccine delivery vehicles is opening up new possibilities for making immunization more equitable, safe and efficient. In this work, we purpose polysaccharidic-based nanoparticles as delivery structures for virus-like particle antigens, using recombinant hepatitis B surface antigen (rHBsAg) as a model. Polysaccharidic-based nanoparticles were prepared using a very mild ionic gelation technique, by cross-linking the polysaccharide chitosan (CS) with a counter ion. The resulting nanoparticles could be easily isolated with a size in the nanometric range (160–200 nm) and positive surface charge (+6 to +10 mV). More importantly, CS-based nanoparticles allowed the efficient association of the antigen (>60%) while maintaining the antigenic epitope intact, as determined by ELISA and Western blot. The entrapped antigen was further released in vitro from the nanoparticles in a sustained manner without compromising its antigenicity. In addition, loaded CS-based nanoparticles were stable, and protected the associated antigen during storage, either as an aqueous suspension under different temperature conditions (+4 °C and −20 °C), or as a dried form after freeze-drying the nanoparticles. Finally, immunization studies showed the induction of important seroprotection rates after intramuscular administration of the nanoparticles, indicating their adjuvant capacity. In fact, CS-based nanoparticles were able to induce anti-HBsAg IgG levels up to 5500 mIU/ml, values 9-fold the conventional alum-adsorbed vaccine. In conclusion, we report here a polysaccharidic nanocarrier which exhibits a number of in vitro and in vivo features that make it a promising adjuvant for vaccine delivery of subunit antigens.