Nasal immunization study by PLGA nanospheres encapsulated with tetanus toxoid and CpG-ODN

In induction of systemic and mucosal immunity, particulate antigens are more effective than soluble antigens; possibly because they are more efficiently endocytosed by mucosal-associated lymphoid tissue (MALT) M cells. In this study, we determined the systemic and mucosal immune responses in rabbits following intranasal immunization of tetanus toxoid (TT) and CpG-ODN encapsulated within PLGA nanospheres. The mean diameter of (TT) and (TT+CpG) nanospheres were 753 ± 193 and 684 ± 324 nm, respectively. Encapsulation efficiency of TT and CpG-ODN was determined as 52 ± 7.8% and 30.2 ± 7.4%, respectively. The highest nasal lavage sIgA titers were observed in groups immunized with nanosphere formulations, while the IgG and antitoxin titers were suppressed by these formulations. CpG-ODN as an adjuvant could increase the serum IgG and antitoxin titers when co-administered with TT solution or co-encapsulated with TT in PLGA nanospheres, but failed to potentiate the IgA titers in nasal lavages. No hemolysis was occurred on incubation of PLGA nanospheres and human RBCs. Also after nasal administration of plain nanospheres to human volunteers, no local irritation was seen. Intranasal administration of nanospheres encapsulated with vaccines showed to be an effective way for inducing mucosal (sIgA) immune responses, and CpG-ODN could increase the systemic immune responses.

Keywords:

Nasal immunization , PLGA , CpG-ODN , nanosphere , tetanus toxoid