Binding immune-stimulating oligonucleotides to cationic peptides from viral core antigen enhances their potency as adjuvants.
Priming specific Th1 immunity by recombinant hepatitis B core antigen (HBcAg) depends on its arginine (Arg)-rich, 34-36-residue-long C terminus, and nucleotides bound to it. This adjuvant activity intrinsic to HBcAg facilitates priming of Th1 immunity to co-delivered, unrelated antigens, such as hepatitis B surface antigen (HBsAg), or ovalbumin (OVA) that prime specific Th2 immunity when injected without adjuvants. We loaded immune-stimulating, CpG-containing oligodeoxynucleotides (ODN) to the HBcAg-derived Arg-rich peptides C-1 (HBcAg(150-157), RRRDRGRS) or C-2 (HBcAg(164-179), SPRRRRSQSPRRRRSQ). When these peptide/nucleotide complexes were co-injected into mice with HBsAg, hepatitis B precore antigen (HBeAg) or OVA, the animals developed strikingly higher serum IgG2 antibody titers and cytotoxic T lymphocyte responses than animals co-injected with these antigens and 'free' (not peptide-bound) ODN. Potent Th1-promoting adjuvants can thus be synthesized that mimic priming of anti-viral immunity by natural nucleocapsid particles.
Institute for Medical Microbiology and Immunology, University of Ulm, Ulm, Germany.
Petra
P
Riedl
Michael
M
Buschle
Jörg
J
Reimann
Reinhold
R
Schirmbeck
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D006512:Hepatitis B Core Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D009841:Oligonucleotides; D010446:Peptide Fragments