The potential of oligodeoxynucleotides as mucosal and parenteral adjuvants.
Synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG ODN) are potent adjuvants in mice when delivered by parenteral (intramuscular, subcutaneous) and mucosal (intranasal, oral and intrarectal) routes. We have recently shown that with mucosal delivery non-CpG ODN can also have immunostimulatory properties which, in contrast to the Th1-bias characteristic of CpG ODN, are predominantly Th2-like. Herein, using hepatitis B surface antigen (HBsAg) and tetanus toxoid (TT) as model antigens in BALB/c mice, we have examined a number of different ODN (CpG, non-CpG, poly-T, poly-CG) to determine their effects on immune responses after mucosal (oral) and parenteral (IM) immunizations. Our findings demonstrate that with mucosal delivery, there is a Th2-biased immunostimulatory effect that is associated with non-CpG ODN, and that the presence of CpG motifs can shift this towards a Th1 response. The adjuvant effect of non-CpG ODN was much less evident after parenteral immunization.
McCluskie
M J
MJ
Loeb Health Research Institute at the Ottawa Hospital, 725 Parkdale Avenue, K1Y 4E9, Ottawa, Canada.
Weeratna
R D
RD
Davis
H L
HL
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000284:Administration, Oral; D000818:Animals; D001483:Base Sequence; D018899:CpG Islands; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018928:Immunity, Mucosal; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D006514:Hepatitis B Surface Antigens; D009838:Oligodeoxyribonucleotides; D013745:Tetanus Toxoid; D014612:Vaccines