Biodegradable nanoparticle delivery of a Th2‐biased peptide for induction of Th1 immune responses

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.