Oral, intrarectal and intranasal immunizations using CpG and non-CpG oligodeoxynucleotides as adjuvants

We have previously demonstrated that synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG ODN) are potent adjuvants in m ice when delivered by intramuscular, intranasal and subcutaneous routes. He rein, using tetanus toroid (TT) as a model antigen in BALB/c mice, we compa red the ability of CpG ODN to induce mucosal and systemic humoral immune re sponses when antigen was delivered by three different routes: intrarectal, intranasal and oral. Results showed differences in immune responses with th e three routes and also revealed that non-CpG "control" ODN had adjuvant ef fects when used at mucosal sites. This was unexpected since non-CpG ODN do not have such immunostimulatory effects in vitro or after parenteral immuni zation. These findings were further investigated after oral delivery of a k illed influenza vaccine on its own as well as combined with TT and hepatiti s B surface antigen. Our findings demonstrate that with mucosal delivery, t here is a Th2 immunostimulatory effect associated with the phosphorothioate ODN backbone, and that the presence of CpG motifs shifts this towards a Th 1 response. (C) 2000 Elsevier Science Ltd. All rights reserved.