[1]秦竹,陈瑾,侯立婷,等.包裹有CTA1-DD蛋白的OCS-DS纳米颗粒的制备及佐剂活性[J].江苏农业学报,2024,(01):141-148.[doi:doi:10.3969/j.issn.1000-4440.2024.01.015]
　QIN Zhu,CHEN Jin,HOU Li-ting,et al.Preparation and adjuvant activity of OCS-DS nanoparticles encapsulating CTA1-DD protein[J].,2024,(01):141-148.[doi:doi:10.3969/j.issn.1000-4440.2024.01.015]
点击复制

包裹有CTA1-DD蛋白的OCS-DS纳米颗粒的制备及佐剂活性()
分享到：

江苏农业学报[ISSN:1006-6977/CN:61-1281/TN]

卷:
期数:
2024年01期
页码:
141-148
栏目:
畜牧兽医·水产养殖·益虫饲养
出版日期:
2024-01-30

文章信息/Info

Title:
Preparation and adjuvant activity of OCS-DS nanoparticles encapsulating CTA1-DD protein
作者:
秦竹1; 2; 陈瑾1; 2; 侯立婷1; 2; 乔绪稳1; 2; 李兰1; 2; 杨利1; 2; 杜露平1; 2; 于晓明1; 2; 张元鹏1; 2; 郑其升1; 2
(1.江苏省农业科学院动物免疫工程研究所/国家兽用生物制品工程技术研究中心/江苏省食品质量与安全重点实验室,江苏南京210014；2.兽用生物制品国泰技术创新中心,江苏泰州225300)
Author(s):
QIN Zhu1; 2; CHEN Jin1; 2; HOU Li-ting1; 2; QIAO Xu-wen1; 2; LI Lan1; 2; YANG Li1; 2; DU Lu-ping1; 2; YU Xiao-ming1; 2; ZHANG Yuan-peng1; 2; ZHENG Qi-sheng1; 2
(1.Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Sciences/National Research Center of Engineering and Technology for Veterinary Biologicals/Jiangsu Key Laboratory for Food Quality and Safety, Nanjing 210014, China；2.Guotai Center of Technology Innovation for Veterinary Biologicals, Taizhou 225300, China)
关键词:
CTA1-DD蛋白; O-羧甲基壳聚糖; 硫酸葡聚糖; 纳米颗粒; 佐剂活性
Keywords:
CTA1-DD protein; O-carboxymethyl chitosan; dextran sulfate; nanoparticles; adjuvant activity
分类号:
S852.4
DOI:
doi:10.3969/j.issn.1000-4440.2024.01.015
文献标志码:
A
摘要:
重组CTA1-DD蛋白具有与完整CT分子相当的全身性和黏膜佐剂功能,但在复杂的生理环境中易被酶或酸降解。本研究以同样具有佐剂活性的O-羧甲基壳聚糖(OCS)和硫酸葡聚糖(DS)为载体,通过离子交联形成纳米颗粒,将CTA1-DD蛋白嵌入其中,使其得到稳定保护。包裹有CTA1-DD蛋白的OCS-DS纳米颗粒的粒径为50～150 nm,Zeta电位约-50 mV,质量浓度1.0 mg/ml的CTA1-DD蛋白投入制备的包裹有CTA1-DD蛋白的OCS-DS纳米颗粒载药率25.33%,包封率86.56%。体外模拟释放试验结果显示CTA1-DD蛋白可在7 d内缓慢释放。将CTA1-DD蛋白与PRV灭活抗原混合后,接种至小鼠鼻腔,结果表明,包裹有CTA1-DD蛋白的OCS-DS纳米颗粒能够同时诱导更高的血清IgG抗体和黏膜IgA抗体表达,证明了其作为黏膜佐剂的高效性。
Abstract:
The recombinant CTA1-DD protein has systemic and mucosal adjuvant functions comparable to intact CT molecules. But it is easily degraded by enzymes or acids in complex physiological environments. In this study, O-carboxymethyl chitosan (OCS) and dextran sulfate (DS), which also had adjuvant activity, were used as carriers to form nanoparticles through ion crosslinking, and CTA1-DD protein was embedded in them for stable protection. The particle size of OCS-DS nanoparticles encapsulating CTA1-DD protein ranged from 50 nm to 150 nm, with a Zeta potential of approximately -50 mV. The drug loading rate of OCS-DS nanoparticles encapsulating CTA1-DD protein was 25.33% when 1.0 mg/ml CTA1-DD protein was put into preparation, and the protein encapsulation rate was 86.56%. The simulated release tests in vitro showed that CTA1-DD protein could be slowly released within seven days. The mice were inoculated intranasally with the mixture of CTA1-DD protein and PRV inactivated antigen. The results showed that OCS-DS nanoparticles encapsulated with CTA1-DD protein could simultaneously induce higher expression of serum IgG antibodies and mucosal IgA antibodies, which proved its high efficiency as mucosal adjuvant.

参考文献/References:

[1]FANG Y, ZHANG T, LIDELL L,et al. The immune complex CTA1-DD/IgG adjuvant specifically targets connective tissue mast cells through FcγRIIIA and augments anti-HPV immunity after nasal immunization[J]. Mucosal Immunol,2013,6(6):1168-1178.
[2]MCNEAL M M, BASU M, BEAN J A, et al. Intrarectal immunization of mice with VP6 and either LT(R192G) or CTA1-DD as adjuvant protects against fecal rotavirus shedding after EDIM challenge[J]. Vaccine,2007,25(33):6224-6231.
[3]SUNDLING C, SCHN K, MRNER A, et al. CTA1-DD adjuvant promotes strong immunity against human immunodeficiency virus type 1 envelope glycoproteins following mucosal immunization[J]. Journal of General Virology,2008,89(12):2954-2964.
[4]FAN X, SU Q, QIU F, et al. Intranasal inoculate of influenza virus vaccine against lethal virus challenge[J]. Vaccine,2018,36(29):4354-4361.
[5]SU Q D, HE S H, YI Y, et al. Intranasal vaccination with ebola virus GP amino acids 258-601 protects mice against lethal challenge[J]. Vaccine,2018,36(41):6053-6060.
[6]GIULIANI M M, DEL-GIUDICE G, GIANNELLI V, et al. Mucosal adjuvanticity and immunogenicity of LTR72, a novel mutant of Escherichia coli heat-labile enterotoxin with partial knockout of ADP-ribosyltransferase activity[J]. Journal of Experimental Medicine,1998,187(7):1123-1132.
[7]TAKAI T, ONO M, HIKIDA M, et al. Augmented humoral and anaphylactic responses in Fc gamma RII-deficient mice[J]. Nature,1996,379(6563):346-349.
[8]周佳升,潘熙,李云香,等. 壳聚糖及其衍生物作为疫苗佐剂研究进展[J]. 动物医学进展,2020,41(4):104-109.
[9]FERREIRA S S, PASSOS C P, MADUREIRA P, et al. Structure-function relationships of immunostimulatory polysaccharides:a review[J]. Carbohydrate Polymers,2015,132:378-396.
[10]邹兴龙,陈柱先,孙娟娟,等. 壳聚糖药用制剂及其应用的研究进展[J]. 基础医学与临床,2022,42(11):1791-1794.
[11]WANG F, ZHANG R, WU Q, et al. Probing the nanostructure,interfacial interaction,and dynamics of chitosan-based nanoparticles by multiscale solid-state NMR[J]. ACS Applied Materials & Interfaces,2014,6(23):21397-21407.
[12]ILLUM L, JABBAL-GILL I, HINCHCLIFFE M, et al. Chitosan as a novel nasal delivery system for vaccines[J]. Advanced Drug Delivery Reviews,2001,51(1/2/3):81-96.
[13]ZAHAROFF D A, ROGERS C J, HANCE K W, et al. Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination[J]. Vaccine,2007,25(11):2085-2094.
[14]SAHARIAH P, MSSON M. Antimicrobial chitosan and chitosan derivatives:a review of the structure-activity relationship[J]. Biomacromolecules,2017,18(11):3846-3868.
[15]KOPPOLU B, ZAHAROFF D A. The effect of antigen encapsulation in chitosan particles on uptake,activation and presentation by antigen presenting cells[J]. Biomaterials,2013,34(9):2359-2369.
[16]DASH M, CHIELLINI F, OTTENBRITE R M, et al. Chitosan-A versatile semisynthetic polymer in biomedical applications[J]. Progress in Polymer Science,2011,36:981-1014.
[17]SAKLOETSAKUN D, PERERA G, HOMBACH J, et al. The impact of vehicles on the mucoadhesive properties of orally administrated nanoparticles:a case study with chitosan-4-thiobutylamidine conjugate[J]. AAPS PharmSciTech,2010,11(3):1185-1192.
[18]GNBEYAZ M, FARAJI A, OZKUL A, et al. Chitosan based delivery systems for mucosal immunization against bovine herpesvirus 1 (BHV-1) [J]. European Journal of Pharmaceutical Sciences,2010,41(3/4):531-545.
[19]ZHAO K, ZHANG Y, ZHANG X, et al. Preparation and efficacy of Newcastle disease virus DNA vaccine encapsulated in chitosan nanoparticles[J]. International Journal of Nanomedicine,2014,9:389-402.
[20]SOTO E, KIM Y S, LEE J, et al. Glucan particle encapsulated rifampicin for targeted delivery to macrophages [J]. Polymers,2010,2(4):681-689.
[21]TSONI S V, BROWN G D. Beta-glucans and dectin-1 [J]. Annals of the New York Academy of Science,2008,1143:45-60.
[22]KIM H S, HONG J T, KIM Y, et al. Stimulatory effect of β-glucans on immune cells [J]. Immune Network,2011,11(4):191-195.
[23]SPANGLER B D. Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin[J]. Clinical Microbiology Reviews,1992,56(4):622-647.
[24]MURAT K, YAVUZ S C, TALAT B, et al. New chitin, chitosan, and O-carboxymethyl chitosan sources from resting eggs of Daphnia longispina (Crustacea); with physicochemical characterization, and antimicrobial and antioxidant activities[J]. Biotechnology and Bioprocess Engineering,2014,19(1):58-69.
[25]LEVINE M M. Can needle-free administration of vaccines become thenorm in global immunization? [J]. Nature Medicine,2003,9(1):99-103.
[26]YUKI Y, KIYONO H. New generation of mucosal adjuvants for the induction of protective immunity[J]. Reviews in Medical Virology,2003,13(5):293-310.

备注/Memo

备注/Memo:
收稿日期:2022-12-20基金项目:江苏省农业科技自主创新基金项目[CX(21)3135]；十四五重点研发专项(2022YFD1800800)作者简介:秦竹(1983-),女,江苏南京人,博士,副研究员,主要从事免疫增强性分子结构设计及其纳米结构研究。(E-mail)qinz@jaas.ac.cn通讯作者:张元鹏,(E-mail)zhangyuanpengnj@163.com；郑其升,(E-mail)njcvc1302@163.com
更新日期/Last Update: 2024-03-17