Controlled release of PEI/DNA complexes from PLGA microspheres as a potent delivery system to enhance immune response to HIV vaccine DNA prime/MVA boost regime

A novel approach involving the preparation of biodegradable PLGA microspheres containing entrapping complexes of DNA and polyethylenimine was developed to improve the delivery of DNA into antigen-presenting cells after intramuscular injection. Compared to the traditional biodegradable microspheres which release naked DNA, these microspheres released intact and penetrative PEI/DNA complexes over a period of 2 weeks in vitro. In addition, the DNA was not degraded during encapsulation in the PLGA microspheres, owing to the protection of polyethylenimine. After i.m. immunization, the microspheres induced significantly enhanced serum antibody responses 2–3 orders of magnitude greater than naked DNA. Additionally, in contrast to naked DNA, the microspheres induced potent CTL responses at a low dose.