Binding immune-stimulating oligonucleotides to cationic peptides from viral core antigen enhances their potency as adjuvants

Abstract

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 (HBcAg150-157, RRRDRGRS) or C-2 (HBcAg164-179, 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 lgG2 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.