Antibody production by administration of biodegradable granules incorporating antigen through different injection routes

Biodegradable poly(DL-lactic acid) granules containing ovalbumin (OVA), a model antigen, were administered by intraperitoneal, subcutaneous, and intramuscular injection to mice to assess the effect of their injection route on the production of OVA-specific antibody in serum. OVA was released in vitro from the OVA-loaded granules over 35 days without any initial burst. A single injection of the granules enhanced the serum level of anti-OVA IgG antibody at an early stage to a great extent compared with that of OVA injection in the water-soluble, free form, although the titer level induced by their intraperitoneal injection was higher than that of other injection routes. The time course of antibody production induced by the granules was independent of the injection route and the enhanced antibody production lasted over a time period of 22 weeks, which was much longer than that of free OVA injection. A body distribution study demonstrated that the injection of OVA incorporated into the granules reduced the serum concentration compared with that of free OVA injection, irrespective of the injection route. It is likely that the granules remained as a depot to gradually release OVA around their injection site, leading to a high adjuvant effect for the enhanced antibody production. In addition, a strong secondary response was observed for every mouse given the primary immunization of the OVA-loaded granules compared with that of free OVA injection, irrespective of their injection route. It was concluded that the granule is a promising immunological adjuvant not only to enhance the antibody production but also to prolong the production.