title: Single low-dose un-adjuvanted HBsAg nanoparticle vaccine elicits robust, durable immunity.
abstract: Chitosan nanoparticles were evaluated as a vaccine delivery system for hepatitis B surface antigen (HBsAg) in the absence of adjuvant. Nano-encapsulated HBsAg (HBsAg chitosan-NP) was endocytosed more rapidly and efficiently by dendritic cells compared to soluble HBsAg. FRET analysis demonstrated that intact nanoparticles were taken up by DCs. To determine the immunogenicity of adjuvant-free nano-encapsulated HBsAg, mice were immunized with a single dose of non-encapsulated HBsAg, HBsAg chitosan-NP, or HBsAg alum. Mice immunized with adjuvant-free nanoparticle elicited anti-HBs antibodies at significantly higher titers compared to mice immunized with HBsAg alum. Elevated numbers of BAFF-R(+) B cells and CD138+ plasma cells account for the heightened anti-HBs response in nanoparticle immunized mice. Increases in Tfh cells provide a mechanism for the accumulation of anti-HBs secreting cells. Thus, chitosan nanoparticle vaccines represent a promising un-adjuvanted platform to generate robust and durable immunity to HBsAg and other subunit antigens following a single low-dose administration.
  
  
  BACKGROUND
  In this study, chitosan nanoparticle vaccines are demonstrated as a promising un-adjuvanted platform to generate robust and durable immunity to HBsAg and other subunit antigens following a single low-dose administration in a murine model. The authors also demonstrated superior antibody response induction compared with non-encapsulated HBs antigen and HBsAg aluminum.
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA.
authors.forename: Amit A
authors.initials: AA
authors.lastname: Lugade
authors.forename: Dhruba J
authors.initials: DJ
authors.lastname: Bharali
authors.forename: Vandana
authors.initials: V
authors.lastname: Pradhan
authors.forename: Galina
authors.initials: G
authors.lastname: Elkin
authors.forename: Shaker A
authors.initials: SA
authors.lastname: Mousa
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Thanavala
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry; D003713:Dendritic Cells / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006509:Hepatitis B / Q000097:blood / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D007109:Immunity / Q000276:immunology*; D007114:Immunization; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010641:Phenotype
chemical_list: D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D048271:Chitosan
keywords: Adjuvant-free; Anti-HBs; HBsAg; Nanoparticle; Vaccine