title: Biodegradable nanoparticle delivery of a Th2-biased peptide for induction of Th1 immune responses.
abstract: The type of immune response developed against the hepatitis B virus (HBV) is crucial in determining the outcome of the disease. The protective effects of vaccine-induced antibody responses against subsequent exposure to HBV are well-established. After the establishment of chronic HBV infection, cell-mediated immune response is curative while humoral response is detrimental. A therapeutic vaccine that could switch the type of response could lead to disease resolution. Hepatitis B core antigen (HBcAg)(129-140) has been identified as a Th2-biased peptide in H-2(b) mice when it is administered along with complete Freund's adjuvant (CFA). We formulated HBcAg(129-140) along with monophosphoryl lipid A in poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles. Naive mice immunized with the nanoparticle formulation developed a strong Th1-type response while mice immunized with the control formulation of CFA and peptide did not. We then primed mice with CFA and peptide to establish a Th2-type immune response before administering the nanoparticle formulation. Mice receiving the nanoparticle formulation being primed with CFA still developed a strong Th1-type response, while mice that received incomplete Freund's adjuvant and peptide instead of nanoparticles did not. The ability of PLGA nanoparticles to alter the type of immune response elicited by a peptide, even in the context of an ongoing immune response, makes PLGA nanoparticles a strong candidate for the formulation of therapeutic vaccines.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.
authors.forename: M E Christine
authors.initials: ME
authors.lastname: Lutsiak
authors.forename: Glen S
authors.initials: GS
authors.lastname: Kwon
authors.forename: John
authors.initials: J
authors.lastname: Samuel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D006512:Hepatitis B Core Antigens / Q000008:administration & dosage*; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D019344:Lactic Acid / Q000008:administration & dosage; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D049329:Nanostructures; D010446:Peptide Fragments / Q000276:immunology*; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D006512:Hepatitis B Core Antigens; D008050:Lipid A; D010446:Peptide Fragments; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma; C048436:monophosphoryl lipid A