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-2b mice when it is administered along with complete Freund's adjuvant (CFA). We formulated HBcAg129–140 along with monophosphoryl lipid A in poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles. Naïve 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.