以乙肝核心抗原病毒样颗粒为新型载体蛋白制备流脑多糖结合疫苗
Preparation of meningococcal polysaccharide conjugate vaccine using Hepatitis B core antigen virus-like particles as a novel carrier protein
作者：胥玲玲;李正军;苏志国;杨延丽;余蓉;郑永祥;张松平;
Author：
收稿日期： 年卷（期）页码：2018,33(06):-463-467
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：流行性脑脊髓膜炎;C群脑膜炎多糖;乙肝核心抗原;病毒样颗粒;结合疫苗;载体蛋白;免疫活性
Key words：
基金项目：国家自然科学基金资助项目(批准号:21336010、81773623)
中文摘要
目的以乙肝核心抗原(HBc)病毒样颗粒为载体,化学偶联脑膜炎奈瑟球菌荚膜多糖,制备高免疫原性的多糖结合疫苗。方法将双功能聚乙烯二醇对C群脑膜炎多糖衍生化后,与巯基化的乙肝核心抗原连接,采用凝胶过滤色谱纯化得到多糖结合疫苗。对结合疫苗的结构表征和多糖含量进行定量分析后,皮下免疫BALB/c小鼠,采用酶联免疫吸附法(ELISA)评价免疫效果。结果衍生化多糖与巯基化的HBc按质量比1∶1投料,在4℃下反应48 h,得到多糖蛋白比为0. 69、游离多糖含量为14. 66%的多糖结合疫苗,并且能够保持HBc完整的颗粒结构。免疫后,纯糖免疫组只能够产生有限的抗体滴度,而以HBc为载体的多糖结合疫苗能够诱导产生明显高于纯糖组的抗体滴度。结论采用HBc作为载体蛋白制备多糖结合疫苗,可以显著提高多糖的免疫原性。作为制备流脑多糖结合疫苗的新型载体蛋白,具有较好的研究价值和应用前景。
参考文献
[1] Christensen H,May M,Bowen L,et al. Meningococcal carriage by age:A systematic review and meta-analysis[J]. Lancet Infect Dis,2010,10(12):853-861.
[2] Tontini M,Romano MR,Proietti D,et al. Preclinical studies on new proteins as carrier for glycoconjugate vaccines[J]. Vaccine,2016,34(35):4235-4242.
[3] Pobre K,Tashani M,Ridda I,et al. Carrier priming or suppression:Understanding carrier priming enhancement of anti-polysaccharide antibody response to conjugate vaccines[J]. Vaccine,2014,32(13):1423-1430.
[4] Roose K,De BS,Schepens B,et al. Hepatitis B core-based virus-like particles to present heterologous epitopes[J]. Expert Rev Vaccines,2013,12(2):183-198.
[5] Huang QR,Li DX,Kang AJ,et al. PEG as a spacer arm markedly increases the immunogenicity of meningococcal group Y polysaccharide conjugate vaccine[J]. J Control Release,2013,172(1):382-389.
[6] Yang YL,Li H,Li ZJ,et al. Size-exclusion HPLC provides a simple,rapid,and versatile alternative method for quality control of vaccines by characterizing the assembly of antigens[J].Vaccine,2015,33(9):1143-1150.
[7]王公孝,王学林,许蓉华,等.检测C群脑膜炎球菌结合疫苗中游离多糖含量的脱氧胆酸钠沉淀法的建立[J].国际生物制品学杂志,2014,37(4):161-163.
[8] Donadei A,Balocchi C,Mancini F,et al. The adjuvant effect of TLR7 agonist conjugated to a meningococcal serogroup C glycoconjugate vaccine[J]. Eur J Pharm Biopharm,2016,107:110-119.
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