Co-delivery of viral proteins and a TLR7 agonist from polysaccharide nanocapsules: A needle-free vaccination strategy

被引:68
作者
Vicente, Sara [1 ,2 ]
Peleteiro, Mercedes [3 ]
Diaz-Freitas, Belen [3 ]
Sanchez, Alejandro [2 ,4 ]
Gonzalez-Fernandez, Africa [3 ]
Alonso, Maria J. [1 ,2 ,4 ]
机构
[1] Univ Santiago de Compostela, Ctr Res Mol Med & Chron Dis CIMUS, Santiago De Compostela, Spain
[2] Univ Santiago de Compostela, Dept Pharm & Pharmaceut Technol, Sch Pharm, Santiago De Compostela, Spain
[3] Univ Vigo, Inst Biomed Res IBIV, Biomed Res Ctr CINBIO, Vigo 36310, Spain
[4] Hlth Res Inst Santiago de Compostela IDIS, Santiago De Compostela 15706, Spain
基金
比尔及梅琳达.盖茨基金会;
关键词
Nanocapsules; Hepatitis B; Imiquimod; Co-delivery; Mucosal vaccination; N-TRIMETHYL CHITOSAN; B SURFACE-ANTIGEN; CYTOKINE PRODUCTION; TMC NANOPARTICLES; IMMUNE-RESPONSE; COMPLEMENT; NASAL; CPG; IMMUNIZATION; IMIQUIMOD;
D O I
10.1016/j.jconrel.2013.09.012
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Here we report a new nanotechnology-based nasal vaccination concept intended to elicit both, specific humoral and cellular immune responses. The concept relies on the use of a multifunctional antigen nanocarrier consisting of a hydrophobic nanocore, which can allocate lipophilic immunostimulants, and a polymeric corona made of chitosan (CS), intended to associate antigens and facilitate their transport across the nasal mucosa. The Toll-like receptor 7 (TLR7) agonist, imiquimod, and the recombinant hepatitis B surface antigen (HB), were selected as model molecules for the validation of the concept. The multifunctional nanocarriers had a nanometric size (around 200 nm), a high positive zeta potential (+45 mV) and a high antigen association efficiency (70%). They also exhibited the ability to enter macrophages in vitro and to effectively deliver the associated imiquimod intracellularly, as noted by the secretion of pro-inflammatory cytokines (i.e. IL-6 and TNF-alpha). However, the nanocarriers did not induce the in vitro activation of the complement cascade. Finally, the positive effect of the co-delivery of HB and imiquimod from the nanocapsules was evidenced upon intranasal administration to mice. The nanocapsules containing imiquimod elicited a protective immune response characterized by increasing IgG levels over time and specific immunological memory. Additionally, the levels of serum IgG subclasses (IgG1 and IgG2a) indicated a balanced cellular/humoral response, thus suggesting the capacity of the nanocapsules to modulate the systemic immune response upon nasal vaccination. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:773 / 781
页数:9
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