title: Immunostimulatory CpG oligodeoxynucleotides enhance the immune response to vaccine strategies involving granulocyte-macrophage colony-stimulating factor.
abstract: Immunostimulatory oligodeoxynucleotides containing the CpG motif (CpG ODN) can activate various immune cell subsets and induce production of a number of cytokines. Prior studies have demonstrated that both CpG ODN and granulocyte-macrophage colony-stimulating factor (GM-CSF) can serve as potent vaccine adjuvants. We used the 38C13 murine lymphoma system to evaluate the immune response to a combination of these two adjuvants. Immunization using antigen, CpG ODN, and soluble GM-CSF enhanced production of antigen-specific antibody and shifted production towards the IgG2a isotype, suggesting an enhanced TH1 response. This effect was most pronounced after repeat immunizations with CpG ODN and antigen/GM-CSF fusion protein. A single immunization with CpG ODN and antigen/GM-CSF fusion protein 3 days before tumor inoculation prevented tumor growth. CpG ODN enhanced the production of interleukin-12 by bone marrow-derived dendritic cells and increased expression of major histocompatibility complex class I and class II molecules, particularly when cells were pulsed with antigen/GM-CSF fusion protein. We conclude that the use of CpG ODN in combination with strategies involving GM-CSF enhances the immune response to antigen and shifts the response towards a TH1 response and that this approach deserves further evaluation in tumor immunization approaches and other conditions in which an antigen-specific TH1 response is desirable.
authors.affiliation: University of Iowa Interdisciplinary Graduate Program in Immunology, University of Iowa Department of Internal Medicine, University of Iowa Cancer Center, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Liu
authors.forename: S E
authors.initials: SE
authors.lastname: Newbrough
authors.forename: S K
authors.initials: SK
authors.lastname: Bhatia
authors.forename: C E
authors.initials: CE
authors.lastname: Dahle
authors.forename: A M
authors.initials: AM
authors.lastname: Krieg
authors.forename: G J
authors.initials: GJ
authors.lastname: Weiner
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D017951:Antigen Presentation / Q000187:drug effects*; D000941:Antigens / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D018899:CpG Islands; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology*; D006183:H-2 Antigens / Q000096:biosynthesis; D006433:Hemocyanins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D019496:Cancer Vaccines; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D009838:Oligodeoxyribonucleotides; D014614:Vaccines, Synthetic; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin