Saydam Manolya, Cheng Woei Ping, Palmer Nathan, Tierney Robert, Francis Robert, MacLellan-Gibson Kirsty, Khan Ambreen, Mawas Fatme
Bacteriology Division, National Institute for Biological Standards and Control (NIBSC), MHRA, Potters Bar, Hertfordshire EN6 3QG, UK.
Department of Pharmacy, Pharmacology and Postgraduate Medicine, School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UK.
Vaccine. 2017 Apr 25;35(18):2489-2495. doi: 10.1016/j.vaccine.2017.03.012. Epub 2017 Mar 18.
The use of Soluplus® polymeric micelles as a novel adjuvant for tetanus toxoid (TTxd) in transcutaneous immunisation was evaluated. TTxd was added to Soluplus® polymeric micelles to form TTxd-Soluplus® nano-aggregates with a size of 68nm. Non-adjuvanted TTxd commonly induces very poor antibody response by the transcutaneous route. However, in this study, the use of TTxd-Soluplus® 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® was also much stronger than that from TTxd alone, in a passive transfer experiment in mice. Soluplus® also enhanced the immunogenicity of the toxoid when TTxd-Soluplus® was stored at 4°C for 4weeks, 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®, suggesting that the mechanism for Soluplus® adjuvanticity is through enhanced uptake of the TTxd through the skin. Overall, our findings demonstrated that Soluplus® is an effective novel adjuvant for transcutaneous immunisation.
评估了用聚乙二醇化聚乙烯己内酰胺（Soluplus®）聚合物胶束作为破伤风类毒素（TTxd）经皮免疫新型佐剂的效果。将TTxd添加到Soluplus®聚合物胶束中，形成大小为68nm的TTxd-Soluplus®纳米聚集体。无佐剂的TTxd经皮途径通常诱导的抗体反应很差。然而，在本研究中，使用TTxd-Soluplus®导致对TTxd的抗体反应显著增加，这与在存在胞嘧啶-磷酸-鸟嘌呤寡脱氧核苷酸（CPG-ODNs）佐剂时诱导的反应相似。在小鼠的被动转移实验中，TTxd-Soluplus®诱导的免疫血清的毒素中和效力也比单独使用TTxd强得多。当TTxd-Soluplus®在4°C储存4周时，Soluplus®也增强了类毒素的免疫原性，但在较高温度下则没有。共聚焦显微镜成像显示，当TTxd与Soluplus®结合时，其在皮肤表皮和真皮层中的摄取量要高得多，这表明Soluplus®佐剂作用的机制是通过增强TTxd经皮肤的摄取。总体而言，我们的研究结果表明，Soluplus®是一种有效的经皮免疫新型佐剂。
