title: Enhanced immune response with a combination of alum and biodegradable nanoparticles containing tetanus toxoid.
abstract: The purpose of the study was to determine the synergistic adjuvant effect of sustained release biodegradable nanoparticles in combination with alum. Nanoparticles containing tetanus toxoid (TT) were formulated using a biodegradable polymer, polylactic polyglycolic acid co-polymer (50:50, molecular weight 100000). The immunization studies were carried out subcutaneously in rats. The results were expressed as mean serum anti-TT IgG levels. I'he nanoparticles demonstrated a TT loading of 4% w/w with mean particle diameter of 238 +/- 31 nm. The TT encapsulated in nanoparticles was released slowly under in vitro conditions, with 67.5% cumulative release occurring in 20 days. A single injection of TT-nanoparticles (TT dose = 10 Lf) mixed with TT-Alum (TT dose= 5 Lf) induced a four-fold greater mean serum anti-TT IgG response than a single injection of TT nanoparticles alone (TT dose=15Lf) (2235 +/- 310 vs. 539 +/- 49 microg/ml, mean +/- sem, p = >0.001). In addition, the mean immune response induced with the single injection of combination of nanoparticles and alum was comparable to the two injections of TT-alum alone (5 Lf each dose) given at 3 week intervals IgG = 1998 +/- 333 microg/ ml). Furthermore, the combination induced a peak immune response (IgG = 4215 +/- 546 microg/ml) as early as the first time point at 3 weeks post-immunization. In the case of a TT-alum alone, the animals showed a weaker immune response at 3 weeks and required a second dose of TT-alum to enhance the antibody response. The data thus suggest that the combination of TT-nanoparticles and TT-alum acts as a much better adjuvant than nanoparticles or alum alone. A rapid induction of immune response is useful to curb the spread of communicable diseases in the case of an outbreak.
authors.affiliation: National Institute of Immunology, New Delhi 110 067, India.
authors.forename: R J
authors.initials: RJ
authors.lastname: Raghuvanshi
authors.forename: A
authors.initials: A
authors.lastname: Mistra
authors.forename: G P
authors.initials: GP
authors.lastname: Talwar
authors.forename: R J
authors.initials: RJ
authors.lastname: Levy
authors.forename: V
authors.initials: V
authors.lastname: Labhasetwar
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000534:Alum Compounds / Q000008:administration & dosage*; D000818:Animals; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding / Q000379:methods*; D004357:Drug Synergism; D007074:Immunoglobulin G / Q000097:blood; D007279:Injections, Subcutaneous; D019344:Lactic Acid; D036103:Nanotechnology; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D051381:Rats; D017208:Rats, Wistar; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D001672:Biocompatible Materials; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007074:Immunoglobulin G; D011108:Polymers; D013745:Tetanus Toxoid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C041524:aluminum sulfate