title: CpG ODN 2006 and IL-12 are comparable for priming Th1 lymphocyte and IgG responses in cattle immunized with a rickettsial outer membrane protein in alum.
abstract: Immunostimulatory oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG ODN) stimulate IL-12-dependent Th1 dominated cytokine and enhanced IgG responses when co-delivered with antigen to mice. However, the CpG ODN sequences that are optimal for each mammalian species may differ. Previously, we demonstrated that a CpG ODN containing the GTCGTT motif was optimal for stimulating bovine B cell proliferation, and induced IL-6, IL-12 and IFN-gamma production by peripheral blood mononuclear cells (PBMC). The current study was designed to test the hypothesis that the nuclease resistant phosphorothioate modified ODN 2006 (TCGTCGTTTTGTCGTTTTGTCGTT) would induce antigen-specific type 1 cytokine and enhanced IgG responses similar to those induced by IL-12. To test this adjuvant effect, calves were immunized with Anaplasma marginale major surface protein 2 (MSP2) with alum alone or combined with CpG ODN 2006, non-CpG ODN R2006 or IL-12. MSP2-specific IgG1 and IgG2 responses developed more rapidly in calves given IL-12, ODN 2006 or ODN R2006, but the highest IgG1 titers were obtained in CpG ODN-immunized calves. Antigen-specific lymphocyte proliferation and frequency of IFN-gamma-secreting cells were significantly increased in CpG ODN 2006- or IL-12-treated calves, and antigen-stimulated PBMC from these calves also expressed higher levels of IFN-gamma transcripts and lower levels of IL-4 transcripts. No differences in IL-10 mRNA expression were detected among the groups. These results indicate that CpG ODN 2006 is an effective vaccine adjuvant for stimulating both antibody and IFN-gamma mediated cellular immune responses in cattle.
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, 99164-7040, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guy H
authors.initials: GH
authors.lastname: Palmer
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Abbott
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Howard
authors.forename: Jayne C
authors.initials: JC
authors.lastname: Hope
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Brown
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000737:chemistry; D000709:Anaplasma / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D008297:Male; D009841:Oligonucleotides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; D007074:Immunoglobulin G; D009841:Oligonucleotides; D012333:RNA, Messenger; C450839:p44 protein, Anaplasma phagocytophila; D018664:Interleukin-12; C041524:aluminum sulfate; D007371:Interferon-gamma