Adamantylamide dipeptide as effective immunoadjuvant in rabbits and mice

In the search for more potent and less toxic immunomodulators, adamantylami de dipeptide (AdDP) was synthesized by the covalent union of amantadine wit h the L-alanyl-D-isoglutamine residue of muramyldipeptide (MDP). The presen t experiments demonstrate the ability of AdDP, co-administered with a prote in immunogen, to raise or enhance a humoral response in immunized animals. BALB/c mice were immunized either by the intraperitoneal (ip) or oral route with ovalbumin (Ova) alone or combined with either AdDP or CpG oligonucleo tide (ODN-CpG), a proved adjuvant. A clear adjuvant dose-response relations hip was observed on the increment of Ova-specific serum antibody titers whe n AdDP was used as adjuvant, irrespectively of the administration route. Th e IgG isotype analysis showed that AdDP promotes a consistent increment in IgG1 antibodies associated with a dominant Th2 response pattern. When admin istered by the oral route, AdDP was at least as efficient as ODN-CpG as adj uvant. Similar results were obtained in rabbits immunized by the oral route , suggesting that the adjuvanticity of AdDP is not restricted to the murine system. In conclusion, AdDP was shown to be a powerful and non-toxic adjuv ant at both systemic and mucosal levels, which makes it a promising tool fo r vaccine development. (C) 2001 Elsevier Science Ltd. All rights reserved.