Immunostimulatory CpG motifs trigger a T helper-1 immune response to human immunodeficiency virus type-1 (HIV-1) gp 160 envelope proteins.
Bacterial DNA sequences containing unmethylated CpG motifs have recently been proposed to exhibit immunostimulatory effects on B-, T- and NK cells, leading to the induction of humoral and cell-mediated immune responses. In the present study we investigated the immunomodulatory effects of a CpG-containing oligodeoxynucleotide (CpG ODN) to the HIV-1 gp 160 envelope (Env) protein in the BALB/c mouse model. Priming and boosting of mice with gp 160 adsorbed to aluminium hydroxide (Alum) induced a typical T helper-2 (Th2)-dominated immune response with high titers of gp 160-specific immunoglobulin (Ig)G1 isotypes but a weak IgG2a response. Specifically re-stimulated splenocytes from these mice predominantly secreted interleukin (IL)-5 but only minute amounts of interferon-gamma (IFN-gamma) upon specific re-stimulation. In contrast, a boost immunisation of gp 160/Alum primed mice with a gp 160/Alum/CpG combination resulted in a seven times higher production of IgG2a antibodies, without affecting the titers of IgG1 isotypes. Furthermore, approximately 10-fold increased levels of IFN-gamma, but significantly reduced amounts of IL-5, were secreted from gp 160-restimulated splenic cells. A further greater than 30-fold increase in the levels of specific IgG2a responses and a substantially elevated secretion of IFN-gamma were observed when the mice received gp160/Alum/CpG combinations for priming and boost injections. Thus, CpG ODNs are useful as an adjuvant to induce a typical Th0/Th1 response to HIV gp 160 proteins. However, despite the induction of a more Th1-like immune response, gp 16O/Alum/CpG combinations were not sufficient to prime an Env-specific cytotoxic T-cell (CTL) response.
Deml
L
L
Institute of Medical Microbiology, University of Regensburg, Germany.
Schirmbeck
R
R
Reimann
J
J
Wolf
H
H
Wagner
R
R
D016915:AIDS Vaccines / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D018899:CpG Islands / Q000235:genetics / Q000276:immunology*; D017931:DNA Primers; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D017931:DNA Primers; D019302:HIV Envelope Protein gp160; D009838:Oligodeoxyribonucleotides