N-Trimethyl chitosan (TMC) nanoparticles loaded with influenza subunit antigen for intranasal vaccination:: Biological properties and immunogenicity in a mouse model
N-Trimethyl chitosan (TMC) nanoparticles loaded with influenza subunit antigen for intranasal vaccination:: Biological properties and immunogenicity in a mouse model
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DOI：
10.1016/j.vaccine.2006.06.086
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发表时间：
2007-01-02
期刊：
影响因子：
5.5
通讯作者：
Jiskoot, Wim
中科院分区：
文献类型：
--
作者：
Amidi, Maryam;Romeijn, Stefan G.;Jiskoot, Wim
在这项研究中，N-三甲基壳聚糖(TMC)纳米粒作为一种单价流感亚单位疫苗鼻腔给药系统的潜力被研究。将含有TMC和甲型流感单价亚基H3N2的溶液与三聚磷酸盐(TPP)溶液混合，在室温和pH 7.4的条件下搅拌，制备抗原负载纳米粒。纳米粒子的平均尺寸约为800 nm，具有窄的尺寸分布和表面正电荷。纳米颗粒的载药率为78%，载药量为13%(w/w)。结果表明，TMC纳米颗粒在PBS中孵育3h后，仍有75%以上的蛋白质与TMC纳米颗粒结合，聚丙烯酰胺凝胶电泳法和Western blotting法分别表明包裹的凝集素具有较高的相对分子质量和抗原性。单一的I.N.或者I.M.负载抗原的TMC纳米粒免疫小鼠后，血凝抑制和总免疫球蛋白应答明显增强。这些反应明显高于肌注后的反应。给予亚单位抗原，而IgG1/IgG2a图谱没有实质性变化。移民局。与其他免疫接种组相比，注射抗原-TMC纳米粒可诱导更高的免疫应答。抗原制剂，这些反应被I.N增强。加强疫苗接种。此外，在测试的配方中，只有I.N.注射含有抗原的TMC纳米颗粒可在所有小鼠的鼻腔冲洗液中诱导显著的IgA水平。综上所述，这些发现表明TMC纳米粒是一种有效的新的I.N递送系统。注射流感抗原。(C)2006爱思唯尔有限公司。保留所有权利。
In this study, the potential of N-trimethyl chitosan (TMC) nanoparticles as a carrier system for the nasal delivery of a monovalent influenza subunit vaccine was investigated. The antigen-loaded nanoparticles were prepared by mixing a solution containing TMC and monovalent influenza A subunit H3N2 with a tripolyphosphate (TPP) solution, at ambient temperature and pH 7.4 while stirring. The nanoparticles had an average size of about 800 nm with a narrow size distribution and a positive surface charge. The nanoparticles showed a loading efficiency of 78% and a loading capacity of 13% (w/w). It was shown that more than 75% of the protein remained associated with the TMC nanoparticles upon incubation of the particles in PBS for 3 h. The molecular weight and antigenicity of the entrapped hemagglutinin was maintained as shown by polyacrylamide gel electrophoresis and Western blotting, respectively. Single i.n. or i.m. immunization with antigen-loaded TMC nanoparticles resulted in strong hemagglutination inhibition and total IgG responses. These responses were significantly higher than those achieved after i.m. administration of the subunit antigen, whereas the IgG1/IgG2a profile did not change substantially. The i.n. administered antigen-TMC nanoparticles induced higher immune responses compared to the other i.n. antigen formulations, and these responses were enhanced by i.n. booster vaccinations. Moreover, among the tested formulations only i.n. administered antigen-containing TMC nanoparticles induced significant IgA levels in nasal washes of all mice. In conclusion, these findings demonstrate that TMC nanoparticles are a potent new delivery system for i.n. administered influenza antigens. (c) 2006 Elsevier Ltd. All rights reserved.