Adjuvant effects of CpG oligodeoxynucleotides on responses against T‐independent type 2 antigens

• Published in: Immunology 2001-01, Vol.102 (1), p.67-76
• Main Authors: Kovarik, J., Bozzotti, P., Tougne, C., Davis, H. L., Lambert, P.‐H., Krieg, A. M., Siegrist, C.‐A.
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic; Aging - immunology; Animals; Antibodies, Bacterial - biosynthesis; Antigens, T-Independent - immunology; B-Lymphocytes - immunology; Carrier Proteins - immunology; CD4-Positive T-Lymphocytes - immunology; CpG Islands - immunology; cytidine phosphate guanosine; Ficoll - analogs & derivatives; Ficoll - immunology; Haptens - immunology; Immunoglobulin G - biosynthesis; immunoglobulin G1; immunoglobulin G2; Immunoglobulin M - biosynthesis; Lymphocyte Activation - immunology; Mice; Mice, Inbred BALB C; oligodeoxynucleotides; Oligonucleotides - immunology; Original; Pneumococcal Vaccines - immunology; Streptococcus pneumoniae - immunology; TI-2 antigen; Trinitrobenzenes - immunology
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1046/j.1365-2567.2001.01158.x

Summary 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 monclonal 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.