Tetanus toxoid microspheres consisting of biodegradable poly(lactide-co-glycolide)- and ABA-triblock-copolymers: immune response in mice.
Tetanus toxoid (TT) was microencapsulated using poly(lactide-co-glycolide) (PLGA) with molar compositions of 50:50, 75:25 or an ABA-triblock-copolymer consisting of PLGA A-blocks attached to a central polyoxyethylene-B-block with a W/O/W (water/oil/water) double emulsion technique. The TT microspheres (MS) were evaluated with respect to protein integrity during antigen release in-vitro and compared with aluminum-adsorbed TT in a mouse model for in-vivo induction of tetanus-specific antibodies as well as protection against a subcutaneous tetanus toxin challenge. The more hydrophilic ABA-triblock-copolymer protected the TT against the deleterious microenvironmental conditions in the degrading MS and provided a prolonged antigen release. In spite of the distinct differences in the in-vitro release patterns MS from PLGA and ABA-triblock-copolymer did not show significant differences in the in-vivo induction of tetanus-specific antibodies. Both preparations elicited antibody titers nearly as high as conventional aluminum-adsorbed TT, which lasted for 29 weeks and were protective against a challenge with 100 x LD(50) tetanus toxin. TT-MS boosted mice which were preimmunized with aluminum-adsorbed as well as with microencapsulated TT. TT-MS are suitable candidates for single shot vaccine delivery systems which elicit a long lasting and protecting immune response.
Jung
Tobias
T
Department of Pharmaceutics and Biopharmacy, Philipps-University of Marburg, Ketzerbach 63, D-35037 Marburg, Germany.
Koneberg
Regina
R
Hungerer
Klaus D
KD
Kissel
Thomas
T
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay; D005079:Excipients; D005260:Female; D007117:Immunization, Secondary; D007700:Kinetics; D019344:Lactic Acid; D051379:Mice; D008863:Microspheres; D010316:Particle Size; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000276:immunology*
D000907:Antibodies, Bacterial; D005079:Excipients; D011108:Polymers; D013745:Tetanus Toxoid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols