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弹性脂质体介导的经皮免疫增强了恶性疟原虫表面抗原MSP-119的免疫原性。

Elastic liposome-mediated transdermal immunization enhanced the immunogenicity of P. falciparum surface antigen, MSP-119.

作者信息

Tyagi Rajeev K, Garg Neeraj K, Jadon Rajesh, Sahu Tejram, Katare Om Prakash, Dalai Sarat K, Awasthi Amit, Marepally Srujan K

机构信息

Department of Periodontics, College of Dental Medicine, Georgia Regents University, Augusta, GA, USA; Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, MP, India.

Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.

出版信息

Vaccine. 2015 Aug 26;33(36):4630-8. doi: 10.1016/j.vaccine.2015.06.054. Epub 2015 Jun 30.

Abstract

Transdermal immunization results in poor immunogenicity, which can be attributed to poor permeability of antigens through the skin. Therefore, elastic liposome, ultradeformable lipid vesicles, may overcome the challenges faced during transdermal immunization. This versatile carrier proves better vehicle for transcutaneous delivery of protein, peptide and nucleic acid antigens. The present results are suggestive of improved immunogenicity of carboxyl-terminal 19 kDa fragment of merozoite surface protein-1 (PfMSP-119) of Plasmodium falciparum when administered subcutaneously through elastic liposomes. The prepared elastic liposomes were characterized with respect to vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, stability and in vitro release. Humoral and cell-mediated immune (CMI) response elicited by topically applied PfMSP-119-loaded elastic liposomes, intramuscularly administered alum-adsorbed PfMSP-119 solution, and topically applied PfMSP-119-loaded conventional liposomes were compared and normalized with vehicle control. Results suggest greater transcutaneous immunization via elastic liposomes, and induced robust and perdurable IgG-specific antibody and cytophilic isotype responses. We report to have achieved sizeable CMI activating factor (IFNγ), a crucial player in conferring resistance to asexual blood stage malaria, responses with elastic liposomes when compared with other formulations. The fluorescence microscopy and histopathology results are suggestive of prominent skin permeation and biodistribution, and demonstrate efficient delivery of malaria antigen via elastic liposomes to immunocompetent Langerhans cells (LC) and lymphatics. In conclusion, elastic liposomal formulation provided greater entrapment efficiency, enhanced penetration and heightened and long-lasting immune response. Moreover, effective immunoadjuvant property of this carrier justifies its potential for improved vaccine delivery, and opens new avenues to explore further on the development of malaria vaccine.

摘要

经皮免疫的免疫原性较差,这可归因于抗原透过皮肤的通透性不佳。因此,弹性脂质体,即超可变形脂质囊泡,可能会克服经皮免疫过程中面临的挑战。这种多功能载体被证明是用于经皮递送蛋白质、肽和核酸抗原的更好媒介。目前的研究结果表明,恶性疟原虫裂殖子表面蛋白-1(PfMSP-119)的羧基末端19 kDa片段通过弹性脂质体皮下给药时,其免疫原性得到了改善。对制备的弹性脂质体在囊泡形状和表面形态、大小和大小分布、包封率、弹性、稳定性和体外释放等方面进行了表征。比较了局部应用负载PfMSP-119的弹性脂质体、肌肉注射明矾吸附的PfMSP-119溶液和局部应用负载PfMSP-119的常规脂质体引发的体液免疫和细胞介导免疫(CMI)反应,并以赋形剂对照进行标准化。结果表明,通过弹性脂质体进行经皮免疫效果更佳,并诱导产生了强大且持久的IgG特异性抗体和嗜细胞同型反应。我们报告称,与其他制剂相比,弹性脂质体在赋予抗无性血液期疟疾抗性方面的关键因素——可观的CMI激活因子(IFNγ)反应方面取得了成效。荧光显微镜和组织病理学结果表明皮肤渗透和生物分布显著,并证明通过弹性脂质体将疟疾抗原有效递送至具有免疫活性的朗格汉斯细胞(LC)和淋巴管。总之,弹性脂质体制剂具有更高的包封率、增强的渗透性以及增强且持久的免疫反应。此外,这种载体有效的免疫佐剂特性证明了其在改善疫苗递送方面的潜力,并为进一步探索疟疾疫苗的开发开辟了新途径。

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