title: Adjuvant effects of CpG oligodeoxynucleotides on responses against T-independent type 2 antigens.
abstract: Oligodeoxynucleotides containing CpG motifs (CpG-ODN) are potent in vitro B-cell activators and they have been successfully used to increase in vivo antibody responses to T-dependent peptide and protein antigens. In contrast, the use of CpG-ODN to enhance in vivo antibody responses to various T-independent type 2 (TI-2) antigens has recently generated contradictory results. In this study, we compared the CpG-ODN stimulatory effect on antibody responses of adult and young BALB/c mice to trinitrophenylaminoethyl-carboxymethyl (TNP) -Ficoll and to polysaccharides (PS) from several distinct serotypes of Streptococcus pneumoniae (SPn). CpG-ODN co-administration significantly enhanced antigen-specific immunoglobulin M (IgM), IgG, IgG1 and IgG2a titres to TNP-Ficoll. The depletion of CD4+ cells by monoclonal antibodies (GK1.5) identified their essential role in CpG-ODN-mediated enhancement of antibody responses. In contrast to TNP-Ficoll, CpG-ODN failed to enhance IgM and IgG responses to any of the 18 SPnPS serotypes tested. Providing T-cell epitopes by the conjugation of SPnPS to the carrier protein tetanus toxoid again allowed CpG-ODN to mediate enhancement of IgG, IgG2a and IgG3 responses to most SPnPS serotypes. Thus, antigen-presenting cell/T-cell interaction appears to largely mediate the in vivo influence of CpG-ODN on antibody responses to TI-2 antigens. In early life, additional factors limit CpG-ODN modulation of antibody responses to TI-2 antigens.
authors.affiliation: World Health Organization Collaborating Centre for Neonatal Vaccinology, C.M.U., Rue Michel Servet 1, CH-1211 Geneva 4, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Kovarik
authors.forename: P
authors.initials: P
authors.lastname: Bozzotti
authors.forename: C
authors.initials: C
authors.lastname: Tougne
authors.forename: H L
authors.initials: HL
authors.lastname: Davis
authors.forename: P H
authors.initials: PH
authors.lastname: Lambert
authors.forename: A M
authors.initials: AM
authors.lastname: Krieg
authors.forename: C A
authors.initials: CA
authors.lastname: Siegrist
mesh_terms: D000276:Adjuvants, Immunologic; D000375:Aging / Q000276:immunology; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000955:Antigens, T-Independent / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D018899:CpG Islands / Q000276:immunology*; D005362:Ficoll / Q000031:analogs & derivatives* / Q000276:immunology; D006241:Haptens / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009841:Oligonucleotides / Q000276:immunology*; D022242:Pneumococcal Vaccines / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000955:Antigens, T-Independent; D002352:Carrier Proteins; D006241:Haptens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009841:Oligonucleotides; D022242:Pneumococcal Vaccines; C020529:TNP-ficoll; D014301:Trinitrobenzenes; D005362:Ficoll