title: CpG ODN can re-direct the Th bias of established Th2 immune responses in adult and young mice.
abstract: Induction of an appropriate immune response is essential for successful immunization. For example, Th1 type immune responses are necessary for the control of intracellular infections whereas Th2 type responses are more useful for the control of extracellular infections. Immunostimulatory CpG ODN (oligonucleotides containing unmethylated cytosine and guanine dinucleotides in specific base contexts) act as potent adjuvants and have been shown to induce Th1 type immune responses with a number of different antigens. This study investigates the effect of CpG ODN on the Th bias of immune responses generated against the hepatitis B major surface antigen (HBsAg) in adult (6-8 weeks old) and young (<1 week old) BALB/c mice. It also investigates the potential of CpG DNA to reverse a pre-established Th2 response generated as an adult or as a neonate, following re-exposure to HBsAg in adult life. Both adult and young mice immunized with HBsAg/CpG ODN had a Th1 biased immune response (strong cytotoxic T-lymphocyte (CTL) induction, IgG2a>>IgG1). In contrast, mice immunized with HBsAg/alum had a Th2 type immune response (poor CTL, IgG1>>IgG2a). More importantly, when animals were immunized with HBsAg/alum and boosted with HBsAg/CpG ODN, the CpG ODN were able to re-direct the Th2 response pre-established by alum, whereas the animals receiving the primary immunization with HBsAg/CpG ODN and later boosted with HBsAg/alum maintained their Th1 bias, even after the boost with alum. These data suggest that CpG ODN have the ability to augment both humoral and cell mediated immune responses and override the Th2 bias created by alum, even in very young animals, which are known to have a Th2 biased immune system.
authors.affiliation: Coley Pharmaceutical Canada, Ottawa, ON, Canada. rweeratna@coleypharma.com
authors.forename: R D
authors.initials: RD
authors.lastname: Weeratna
authors.forename: C L
authors.initials: CL
authors.lastname: Brazolot Millan
authors.forename: M J
authors.initials: MJ
authors.lastname: McCluskie
authors.forename: H L
authors.initials: HL
authors.lastname: Davis
mesh_terms: D000276:Adjuvants, Immunologic; D000375:Aging / Q000276:immunology; D000534:Alum Compounds; D000818:Animals; D018899:CpG Islands / Q000276:immunology*; D006509:Hepatitis B / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009841:Oligonucleotides / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D009841:Oligonucleotides