CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity.
Synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG ODN) induce macrophages to secrete IL-12, which induces interferon (IFN)-gamma secretion by natural killer (NK) cells. Since these cytokines can induce T helper 1 (Th1) differentiation, we examined the effects of coadministered CpG ODN on the differentiation of Th responses to hen egg lysozyme (HEL). In both BALB/c (Th2-biased) and B10.D2 (Th1-biased) mice, immunization with HEL in incomplete Freund's adjuvant (IFA) resulted in Th2-dominated immune responses characterized by HEL-specific secretion of IL-5 but not IFN-gamma. In contrast, immunization with IFA-HEL plus CpG ODN switched the immune response to a Th1-dominated cytokine pattern, with high levels of HEL-specific IFN-gamma secretion and decreased HEL-specific IL-5 production. IFA-HEL plus CpG ODN also induced anti-HEL IgG2a (a Th1-associated isotype), which was not induced by IFA-HEL alone. Control non-CpG ODN did not induce IFN-gamma or IgG2a, excepting lesser increases in B10.D2 (Th1-biased) mice. Thus, CpG ODN provide a signal to switch on Th1-dominated responses to coadministered antigen and are potential adjuvants for human vaccines to elicit protective Th1 immunity.
Chu
R S
RS
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Targoni
O S
OS
Krieg
A M
AM
Lehmann
P V
PV
Harding
C V
CV
D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D000918:Antibody Specificity; D002645:Chickens; D018899:CpG Islands / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000276:immunology; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D013873:Thionucleotides / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D000939:Epitopes; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D009838:Oligodeoxyribonucleotides; D013873:Thionucleotides; D009113:Muramidase