SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh 495009, India.
National UGC Centre of Excellence in NanoBiomedical Applications, Panjab University, Chandigarh 160014, India.
J Pharm Sci. 2019 Nov;108(11):3550-3559. doi: 10.1016/j.xphs.2019.07.007. Epub 2019 Jul 23.
Transcutaneous immunization is the administration of a vaccine on the skin to generate efficient systemic and mucosal immune responses against an antigen. In the present study, reconstituted hepatitis B surface antigen vesicles (HBsAg-REVs) integrated with monophosphoryl lipid A were prepared by the delipidation-reconstitution method and tested as built-in adjuvanted vaccine, system for transcutaneous immunization using a combined approach of tape strippings, and enhanced antigen skin contact time. Prepared vesicles were extensively characterized for size, shape, zeta potential, and antigen protein loading efficiency. Following topical application, HBsAg-REVs skin permeation on isolated rat skin and cell uptake by bone marrow-derived dendritic cells were determined by confocal laser scanning microscopy and flow cytometry, respectively. The humoral and cellular immune responses elicited by HBsAg-REVs via transcutaneous immunization were comparable to the marketed intramuscular hepatitis B vaccine formulation with predefined immunization protocols. This study supports that delivery of reconstituted HBsAg vesicles via transcutaneous route may open a new vista for designing topical vaccines with possible immune protection against hepatitis B in future.
经皮免疫是将疫苗施用于皮肤，以针对抗原产生有效的全身和粘膜免疫应答。在本研究中，通过去脂-再酯化方法制备了与单磷酰脂质 A 整合的重组乙型肝炎表面抗原囊泡 (HBsAg-REVs)，并作为内置佐剂疫苗进行了测试，采用联合胶带剥离、增强抗原皮肤接触时间的经皮免疫系统进行了测试。对制备的囊泡进行了广泛的特征分析，包括大小、形状、Zeta 电位和抗原蛋白负载效率。通过共聚焦激光扫描显微镜和流式细胞术分别确定了 HBsAg-REVs 经皮给药后在分离的大鼠皮肤上的渗透以及骨髓来源的树突状细胞的摄取情况。通过经皮免疫接种 HBsAg-REVs 引起的体液和细胞免疫应答与具有预定义免疫方案的市售肌肉内乙型肝炎疫苗制剂相当。这项研究支持通过经皮途径递送重组 HBsAg 囊泡可能为未来设计具有潜在乙型肝炎免疫保护作用的局部疫苗开辟新的前景。
