Induction of potent immune responses by cationic microparticles with adsorbed human immunodeficiency virus DNA vaccines

The effectiveness of cationic microparticles with adsorbed DNA at inducing immune responses was investigated in mice, guinea pigs, and rhesus macaques . Plasmid DNA vaccines encoding human immunodeficiency virus (HIV) Gag and Env adsorbed onto the surface of cationic poly(lactide-coglycolide) (PLG) m icroparticles were shown to be substantially more potent than corresponding naked DNA vaccines. In mice immunized with HIV gag DNA, adsorption onto PL G increased CD8(+) T-cell and antibody responses by similar to 100- and sim ilar to1,000-fold, respectively. In guinea pigs immunized with HIV env DNA adsorbed onto PLG, antibody responses showed a more rapid onset and achieve d markedly higher enzyme-linked immunosorbent assay and neutralizing titers than in animals immunized with naked DNA. Further enhancement of antibody responses was observed in animals vaccinated with PLG/DNA microparticles fo rmulated with aluminum phosphate. The magnitude of anti-Env antibody respon ses induced by PLG/DNA particles was equivalent to that induced by recombin ant gp120 protein formulated with a strong adjuvant, MF-59. In guinea pigs immunized with a combination vaccine containing HIV env and HIV gag DNA pla smids on PLG microparticles, substantially superior antibody responses were induced against both components, as measured by onset, duration, and titer . Furthermore, PLG formulation overcame an apparent hyporesponsiveness of t he env DNA component in the combination vaccine. Finally, preliminary data in rhesus macaques demonstrated a substantial enhancement of immune respons es afforded by PLG/DNA. Therefore, formulation of DNA vaccines by adsorptio n onto PLG microparticles is a powerful means of increasing vaccine potency .