Enhancement of immune responses by co-delivery of a CpG oligodeoxynucleotide and tetanus toxoid in biodegradable nanospheres

摘要: Synthetic oligodeoxynucleotides (ODN) consisting of unmethylated bacterial DNA sequences with CpG motifs are potent immunological adjuvants. Immunostimulatory species-specific. Optimal specific for humans, rodents, livestock, and companion animals have been reported. Nearly all these reports describe the use soluble forms ODN antigens. We investigated co-delivery antigens in biodegradable nanospheres as an alternative approach immunization using tetanus toxoid (TT) model antigen #1826 sequence. TT were co-encapsulated poly(D,L-lactic-co-glycolic acid) nanospheres. Separate groups C57BL/6 mice subcutaneously immunized twice (test group), alone nanospheres, mixed solution, both solution (reference alum adsorbed TT. T cells isolated from test group showed strong antigen-specific cell proliferation ex vivo (stimulation index=45). This was significantly (P<0.0001) higher than that observed reference group. The associated levels interferon gamma secretion (IFN-gamma 2694.7+/-41.1 pg/ml) (814.7+/-50.2 pg/ml). Interleukin 4 (IL-4) secretion, if any, below detection limit (<13 groups. Anti-sera obtained also very high total IgG titers (end point titers, 2560000) 16 times Similarly, differences 8-fold IgG1 IgG3, 5-fold IgG2b observed. Noticeably, antibody response induced alum-TT far less (total IgG, end 160000) TT-CpG Overall, results show resulted induction helper type 1 2 (Th1 Th2) immune responses a bias towards Th1 type. These suggest adjuvants is more efficient solution.