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 100 000). The immunization studies were carried out subcutaneously in rats. The results were expressed as mean serum anti-TT IgG levels. The nanoparticles demonstrated a TT loading of 4% w/w with mean particle diameter of 238 #45 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=15 Lf) (2235 #45 310 vs. 539 #45 49 #119 g/ml, mean #45 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 #45 333 #119 g/ ml). Furthermore, the combination induced a peak immune response (IgG = 4215 #45 546 #119 g/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 TTnanoparticles 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.