Enhancing Mucosal Immune Response of Newcastle Disease Virus DNA Vaccine Using N-2-Hydroxypropyl Trimethylammonium Chloride Chitosan and N,O-Carboxymethyl Chitosan Nanoparticles as Delivery Carrier,Molecular Pharmaceutics

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Enhancing Mucosal Immune Response of Newcastle Disease Virus DNA Vaccine Using N-2-Hydroxypropyl Trimethylammonium Chloride Chitosan and N,O-Carboxymethyl Chitosan Nanoparticles as Delivery Carrier
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-12-06 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00826
Kai Zhao ₁ , Jinyu Han ₂ , Yang Zhang ₁ , Lin Wei ₁ , Shuang Yu ₁ , Xiaohua Wang ₁ , Zheng Jin ₂ , Yunfeng Wang ₃

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Because mucosal sites are the entry ports of pathogens, immunization via mucosal routes can extremely enhance the immunity. To elevate the potential of N-2-hydroxypropyl trimethylammonium chloride chitosan (N-2-HACC) and N,O-carboxymethyl chitosan (CMC) nanoparticles as a mucosal immune delivery carrier for DNA vaccines, we prepared the NDV F gene plasmid DNA with C3d6 molecular adjuvant (pVAX I-F(o)-C3d6) encapsulated in the N-2-HACC-CMC nanoparticles (N-2-HACC-CMC/pFDNA-C3d6 NPs). The N-2-HACC-CMC/pFDNA-C3d6 NPs had regular spherical morphology and low toxicity with a mean diameter of 309.7 ± 6.52 nm, zeta potential of 49.9 ± 4.93 mV, encapsulation efficiency of 92.27 ± 1.48%, and loading capacity of 50.75 ± 1.35%. The N-2-HACC-CMC had high stability and safety. The pVAX I-F(o)-C3d6 could be sustainably released from the N-2-HACC-CMC/pFDNA-C3d6 NPs after an initial burst release. Immunization intranasally of chickens with N-2-HACC-CMC/pFDNA-C3d6 NPs not only produced higher anti-NDV IgG and sIgA antibody than chickens in other groups did, but also significantly stimulated lymphocyte proliferation and triggered higher the IL-2, IL-4, and IFN-γ levels. These findings indicated that the N-2-HACC-CMC could be used as an efficient delivery carrier for the mucosal immunity of Newcastle disease virus DNA vaccine. The work laid a basis for the quaternized chitosan nanoparticles as efficient mucosal immunity delivery carrier for DNA vaccines and had immense application promise and potential for vaccines and drugs.

中文翻译：

N -2-羟丙基三甲基氯化铵壳聚糖和N，O-羧甲基壳聚糖纳米粒子作为递送载体增强新城疫病毒DNA疫苗的粘膜免疫反应

由于粘膜部位是病原体的进入端口，因此通过粘膜途径进行免疫可以极大地增强免疫力。提高N -2-羟丙基三甲基氯化铵壳聚糖（N-2-HACC）和N，O的潜力-羧甲基壳聚糖（CMC）纳米颗粒作为粘膜免疫递送载体用于DNA疫苗，我们制备了带有C3d6分子佐剂（pVAX IF（o）-C3d6）的NDV F基因质粒DNA，并将其包裹在N-2-HACC-CMC纳米颗粒中（ N-2-HACC-CMC / pFDNA-C3d6 NPs）。N-2-HACC-CMC / pFDNA-C3d6 NP具有规则的球形形态和低毒性，平均直径为309.7±6.52 nm，ζ电位为49.9±4.93 mV，包封效率为92.27±1.48％，负载能力为50.75±1.35％。N-2-HACC-CMC具有很高的稳定性和安全性。初始爆发释放后，pVAX IF（o）-C3d6可以从N-2-HACC-CMC / pFDNA-C3d6 NP持续释放。用N-2-HACC-CMC / pFDNA-C3d6 NP对鸡进行鼻内免疫不仅产生了比其他组鸡更高的抗NDV IgG和sIgA抗体，但也能显着刺激淋巴细胞增殖并引发更高的IL-2，IL-4和IFN-γ水平。这些发现表明N-2-HACC-CMC可以用作新城疫病毒DNA疫苗的粘膜免疫的有效传递载体。这项工作为季铵化壳聚糖纳米粒作为DNA疫苗的有效粘膜免疫传递载体奠定了基础，并为疫苗和药物具有广阔的应用前景和潜力。

更新日期：2017-12-06

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