Tetanus toxoid and synthetic malaria antigen containing poly(lactide)/poly(lactide-co-glycolide) microspheres: Importance of polymer degradation and antigen release for immune response

The importance of in vitro degradation of poly(lactide)/poly(lactide-co-glycolide) (PLA/PLGA) microspheres and of the concomitant in vitro release of a natural and a synthetic antigen for eliciting immune response was studied in mice. A variety of PLAs and PLGAs differing in molecular weight (<(M)over bar (w)> of 14-130 kDa) and in polymer composition (lactic/glycolic acid ratio of 100:00, 75:25, and 50:50) were examined for their in vitro degradation, which ranged from approximately 4 to 20 weeks. Three specific polymers were then selected for microencapsulation of the two antigens tetanus toroid (TT) and a weakly immunogenic synthetic branched malaria peptide (P30B2). The in vitro release data showed that antigen delivery correlates fairly well with polymer degradation giving rise to a distinct burst release during the first 24 h and an additional release pulse towards the end of polymer degradation. After single subcutaneous administration in mice, long lasting high antibody titers were obtained with the antigen containing microspheres, as compared to TT adsorbed on alum or to P30B2 in Incomplete Freund's Adjuvant. Moreover, the immune responses induced by microspheres were clearly influenced by the antigen release kinetics, the polymer type and the size of the microspheres. The results demonstrate the immunopotentiating properties of the biodegradable microspheres and their potential to elicit long-lasting immune responses after single administration when tailoring in vitro release characteristics and particle size.