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Paper Information

Journal:   IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES   Fall 2003 , Volume 6 , Number 3 (19); Page(s) 221 To 236.
 
Paper: 

INCREASING THE IMMUNE RESPONSES BY CO-DELIVERY OF CPG-ODN AND TETANUS TOXOID ENCAPSULATED IN PLGA MICROSPHERES

 
 
Author(s):  SAJADI TABASSI S.A., JAFARI M.R., TAFAGHODI M., DIVAN M., SAMUEL J.
 
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Abstract: 

Oligodeoxynucleotides (ODN) having a CpG motif (CpG-ODN) are regarded as a new class of potent immunoadjuvants. It has been shown that concomitant delivery of an antigen with CpG-ODN to the same APC will be able to increase the immune responses against the relevant antigen. The main objective of the present study was co-encapsulation of tetanus toxoid (TT) and CpG-ODN in PLGA microspheres and evaluation of immune responses gained by the concomitant delivery of TT and CpG-ODN via the same delivery system. Both TT alone and [TT+CpG-ODN] were encapsulated in PLGA microspheres. The following groups of mice were immunized twice 2 Lf TT in the presence or absence of 4µg CpG-ODN via subcutaneous route: 1) encapsulated [TT + CpG-ODN]; 2) encapsulated TT alone; 3) encapsulated TT with CpG-ODN solution; 4) solution of [TT+ CpG-ODN]; 5) alum adsorbed TT (routine vaccine). Mice immunized with microspheres encapsulated with [TT+CpG-ODN] showed a very high T cell proliferation (stimulation index=45 in T cell proliferation assay and very high levels of INF-γ (2694.7±41.1 pg/ml) which was significantly higher than those of other groups. Anti-sera obtained from this group also showed very high total IgG titers (end point titers 2560000) which was 16 times that of the group immunized with the solution of [TT+CpG-ODN]. Also the titers of IgGl, IgG3 and IgG2b obtained from group 1 were considerably higher than those from other groups. Interestingly however the IgG titers induced in group 5 were far less than that in group 1 (total IgG, end point titers 160000).

This study clearly showed that [TT+CpG-ODN] encapsulated in PLGA microspheres was more efficient than the relevant solution in terms of inducing immune responses. Also the results indicated that the co-delivery of TT and CpG-ODN in PLGA microspheres elicits a stronger Th1 (i.e. IgG2b, IgG3, INF- γ ) as well as Th2 (i.e. IgG1) type responses.

 

 

 

 

 
Keyword(s): TETANUS TOXOID, CPG, OLIGODEOXYNUCLEOTIDES, MICROSPHERES, ALUM, ADJUVANT
 
References: 
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