Enhanced antibody production through sustained antigen release from biodegradable granules

A proteinaceous model antigen, ovalbumin (OVA), was incorporated into poly(DL-lactic acid) (PDLLA) granules for sustained release of OVA over about 5 weeks without any large initial burst. When the granules were injected into the mouse peritoneal cavity, the production of anti-OVA IgG antibody in the serum was significantly enhanced and persisted for a long period compared with that induced by injection of OVA in the water-soluble form. Simple mixing of the PDLLA granules with free OVA had no enhancing effect on the antibody response, indicating that OVA incorporation in the granules is essential to enhance IgG production. The secondary response to antibody production was greater for mice given the primary immunization with the OVA-loaded granules than with free OVA. A body distribution study of OVA demonstrated that incorporation of OVA into PDLLA granules reduced its translocation to the blood circulation, leading to prolonged accumulation of OVA in the peritoneal cavity. Macrophages cocultivated with PDLLA granules containing OVA produced a larger amount of interleukin 1 than those cultured with other agents, suggesting that the PDLLA granules effectively activate the cell function for antibody production. It was concluded that the biodegradable granules were useful as a release carrier of antigens to enhance the antibody production.