Nano-sized Soluplus® polymeric micelles enhance the induction of tetanus toxin neutralising antibody response following transcutaneous immunisation with tetanus toxoid

The use of Soluplus (R) polymeric micelles as a novel adjuvant for tetanus toxoid (TTxd) in transcutaneous immunisation was evaluated. TTxd was added to Soluplus (R) polymeric micelles to form TTxd-Soluplus (R) nano-aggregates with a size of 68 nm. Non-adjuvanted TTxd commonly induces very poor antibody response by the transcutaneous route. However, in this study, the use of TTxd-Soluplus (R) resulted in a significant increase in the antibody response to TTxd, which was similar to that induced in the presence of CPG-oligodeoxynucleotides (CPG-ODNs) adjuvant. The toxin neutralising potency of the immune sera induced by TTxd-Soluplus (R) was also much stronger than that from TTxd alone, in a passive transfer experiment in mice. Soluplus (R) also enhanced the immunogenicity of the toxoid when TTxd-Soluplus (R) was stored at 4 degrees C for 4 weeks, but not at higher temperatures. Confocal microscopy imaging showed a much higher uptake of TTxd in the epidermis and dermis layers of the skin when it was associated with Soluplus (R), suggesting that the mechanism for Soluplus (R) adjuvanticity is through enhanced uptake of the TTxd through the skin. Overall, our findings demonstrated that Soluplus (R) is an effective novel adjuvant for transcutaneous immunisation. (C) 2017 Elsevier Ltd. All rights reserved.