INDUCTION OF SUSTAINED AND ELEVATED IMMUNE-RESPONSES TO WEAKLY IMMUNOGENIC SYNTHETIC MALARIAL PEPTIDES BY ENCAPSULATION IN BIODEGRADABLE POLYMER MICROSPHERES

Biodegradable microspheres (MS) based on poly (D, L-lactide) and poly (D, L-lactide-co-glycolide) have the capacity to release encapsulated antigens over defined lengths of time depending on their composition a nd to elicit and sustain strong and long-lasting immune responses to p rotein antigens. In the present study, two synthetic multiple antigeni c peptides (MAP), P30B2 and (NANP)(6)P2P30, were incorporated into MS of different compositions. P30B2 and (NANP)(6)P2P30 are composed of on e or two universal T helper epitopes from tetanus toxin, 947-967 (P30) and 830-843 (P2), and of a B cell epitope derived from the repeat seq uence of Plasmodium berghei or Plasmodium falciparum, respectively. BA LB/c mice were immunized with these two peptides in different formulat ions, including individual MS or mixtures of MS with various release p roperties, Incomplete Freund's adjuvant (IFA) or as soluble peptides. MS formulations elicited strong and sustained proliferative and antibo dy responses comparable to those obtained with the IFA preparations. F urthermore, MS formulations induced specific isotyped subclass antibod ies similar to those induced by IFA. No significant augmentation of fe tal serum IgE was detected during this study. In addition, a boosting effect was obtained when the immunized mice were reinjected with a sma ll antigen dose in IFA several months later. These results indicate th at biodegradable MS may be a suitable vaccine delivery system/adjuvant not only for protein antigens but also for weakly immunogenic synthet ic peptides. Copyright (C) 1996 Elsevier Science Ltd.