新型纳米壳聚糖/ DNA复合物诱导抗体应答小鼠乙肝表面抗原的

StephenW

Intranasal Administration of Novel Chitosan Nanoparticle/DNA Complexes Induces Antibody Response to Hepatitis B Surface Antigen in MiceF. Lebre†‡, G. Borchard§, H. Faneca†∥, M. C. Pedroso de Lima†∥, and O. Borges*†‡

† CNC—Centerfor Neuroscience and Cell Biology, Universityof Coimbra, 3004-0504 Coimbra, Portugal
‡ Facultyof Pharmacy, University of Coimbra, Pólo das Ciências da Saúde,Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
§ Schoolof Pharmaceutical Sciences, University ofGeneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva, Switzerland
∥ Departmentof Life Sciences, University of Coimbra, 3004-517 Coimbra, Portugal

Mol. Pharmaceutics, 2016, 13 (2), pp 472–482
DOI: 10.1021/acs.molpharmaceut.5b00707
Publication Date (Web): December 14, 2015
Copyright © 2015 American Chemical Society
*Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. Tel: (351) 239 488428. Fax: (351) 239 488 503. E-mail: [url=mailto[email protected]][email protected][/url].

Abstract

The generation of strong pathogen-specific immune responses at mucosal surfaces where hepatitis B virus (HBV) transmission can occur is still a major challenge. Therefore, new vaccines are urgently needed in order to overcome the limitations of existing parenteral ones. Recent studies show that this may be achieved by intranasal immunization. Chitosan has gained attention as a nonviral gene delivery system; however, its use in vivo is limited due to low transfection efficiency mostly related to strong interaction between the negatively charged DNA and the positively charged chitosan. We hypothesize that the adsorption of negatively charged human serum albumin (HSA) onto the surface of the chitosan particles would facilitate the intracellular release of DNA, enhancing transfection activity. Here, we demonstrate that a robust systemic immune response was induced after vaccination using HSA-loaded chitosan nanoparticle/DNA (HSA-CH NP/DNA) complexes. Furthermore, intranasal immunization with HSA-CH NP/DNA complexes induced HBV specific IgA in nasal and vaginal secretions; no systemic or mucosal responses were detected after immunization with DNA alone. Overall, our results show that chitosan-based DNA complexes elicited both humoral and mucosal immune response, making them an interesting and valuable gene delivery system for nasal vaccination against HBV.

Keywords: chitosan nanoparticles; DNA vaccine; gene delivery; hepatitis B vaccine; nasal immunization

StephenW

新型纳米壳聚糖/ DNA复合物诱导抗体应答小鼠乙肝表面抗原的鼻内管理
F. Lebre†‡，GBorchard§，H法内卡†∥，M. C.佩德罗索利马†∥和O.博尔赫斯*†‡
†CNC-中心神经科学与细胞生物学，科英布拉大学，3004-0504葡萄牙科英布拉
药学院‡，科英布拉大学，POLO科学城达斯达SAUDE，Azinhaga圣京信通信，3000-548葡萄牙科英布拉
§洛桑大学，日内瓦大学药学院，，，的Quai欧内斯特·安塞美30日，1211瑞士日内瓦
生命科学系∥，科英布拉大学，3004-517葡萄牙科英布拉
摩尔。药剂学，2016年，13（2），页472-482
DOI：10.1021 / acs.molpharmaceut.5b00707
出版日期（网络）：2015年12月14日，
版权所有©2015年美国化学学会
*药剂，科英布拉大学，POLO科学城达斯达SAUDE，Azinhaga圣京信通信，3000-548葡萄牙科英布拉学院。电话：（351）239 488428.传真：（351）239 488 503电子邮箱：[email protected]。
抽象
抽象的形象

在粘膜表面可能发生乙型肝炎病毒（HBV）传输强特异性病原体的免疫反应的产生仍是一个重大的挑战。因此，新的疫苗，迫切需要以克服现有肠胃那些的限制。最近的研究表明，这可以通过鼻内免疫来实现。壳聚糖受到关注作为非病​​毒基因传递系统;然而，其在体内使用时由于低转染效率大多与带负电荷的DNA和带正电的脱乙酰壳多糖之间的强的相互作用的限制。我们推测，带负电荷的人血清白蛋白的吸附（HSA）上的脱乙酰壳多糖颗粒的表面将促进DNA的细胞内释放，增强转染活性。在这里，我们证明了一个强大的全身免疫反应接种疫苗后用HSA-壳聚糖纳米颗粒/ DNA（HSA-CH NP / DNA）复合物引起的。此外，HSA-CH NP / DNA复合物鼻内免疫诱导乙型肝炎病毒特异性IgA在鼻和阴道分泌物;单独用DNA免疫后没有检测到全身或粘膜反应。总的来说，我们的结果表明，脱乙酰壳多糖为基础的DNA复合物引起体液和粘膜免疫应答，这使得它们对于抗HBV鼻接种了一个有趣的和有价值的基因递送系统。
关键词：壳聚糖纳米粒; DNA疫苗;基因传递;乙肝疫苗;鼻腔免疫