CHRONIC LOCAL TISSUE-REACTIONS, LONG-TERM IMMUNOGENICITY AND IMMUNOLOGICAL PRIMING OF MICE AND GUINEA-PIGS TO TETANUS TOXOID ENCAPSULATED IN BIODEGRADABLE POLYMER MICROSPHERES COMPOSED OF POLY LACTIDE-CO-GLYCOLIDE POLYMERS

Immunogenicity of tetanus toxoid (TT) encapsulated in biodegradable po lymer microspheres composed of poly lactide (PLA) or poly lactide-co-g lycolide (PLGA) polymers was evaluated in mice and guinea pigs for 1 y ear. Microsphere formulations made from polymers differing in molecula r weight and composition elicited significantly higher IgG antibody le vels than soluble TT in mice. The antibody levels elicited by microsph ere formulations in mice and guinea pigs were similar to those elicite d by a single injection of AlPO4 adsorbed TT. Immunogenicity was not c onsistently better with a particular polymer composition, molecular we ight or microsphere size. However, animals primed with TT-containing m icrospheres showed significantly higher anamnestic response to a low d ose booster 1 year after priming than those primed with AlPO4 adsorbed TT. Microspheres made from low molecular weight PLGA polymer showed a minimal local tissue reaction 1 year after injection. In contrast, al uminum adjuvant formed local granulomas which persisted for 1 year aft er injection. Microsphere formulations used in this study released a s mall fraction of antigenic TT during in vitro release studies due to d enaturation of TT during encapsulation and hydration of microspheres. Nevertheless, strong priming of immune responses were seen. It remains to be demonstrated whether stabilization of TT would lead to more imm unogenic microsphere formulations. (C) 1997 Published by Elsevier Scie nce Ltd.