CpG1826对重组新型冠状病毒亚单位疫苗的协同免疫增强效果研究  

Study on the synergistic immune enhancement effect of CpG1826 on the recombinant subunit vaccine of SARS-CoV-2

作　　者：杨宏宏 沈钱通 李思奇 安彤 于鹏程[2] 张月 徐凯 陈彦霖 陈刚 高孟 庄昉成 Yang Honghong;Shen Qiantong;Li Siqi;An Tong;Yu Pengcheng;Zhang Yue;Xu Kai;Chen Yanlin;Chen Gang;Gao Meng;Zhuang Fangcheng(School of Basic Medical Science and Forensic Medicine,Hangzhou Medical College,Hangzhou 310053,China;Institute of Virology,Chinese Center for Disease Control and Prevention,Beijing 102206,China;Zhejiang Pukang Biotechnology Co.,Ltd.,Hangzhou 310053,China)

机构地区：[1]杭州医学院基础医学与法医学院,310053 [2]中国疾病预防控制中心病毒病研究所,北京102206 [3]浙江普康生物技术股份有限公司,杭州310053

出　　处：《国际流行病学传染病学杂志》2021年第2期93-98,共6页International Journal of Epidemiology and Infectious Disease

基　　金：浙江省自然科学基金应急重大项目(LED20C080002)。

摘　　要：目的以CpG1826作为疫苗佐剂评价其与铝佐剂对大肠埃希菌表达的新型冠状病毒(SARS-CoV-2)亚单位疫苗免疫原性的协同增强效果。方法利用大肠埃希菌高效表达SARS-CoV-2亚单位抗原,纯化后加入CpG1826和铝佐剂。将BALB/c小鼠随机分成铝佐剂疫苗组、CpG+铝佐剂疫苗组和空白对照组,每组18只,于0、7和14 d进行腹腔注射免疫。分别于首针免疫后7、14和28 d采血和取脾检测小鼠血清IgG水平、中和抗体水平以及小鼠脾细胞上清中IFN-γ细胞因子水平。结果在首针免疫28 d后,3组小鼠的IgG、结合抗体抑制率和中和抗体水平差异均有统计学意义(F=21.440、159.400和8.470,P均<0.05),其中CpG+铝佐剂疫苗组分别为6.91±0.20、(91.01±4.60)%和65.33±51.70,均高于铝佐剂疫苗组(t=2.892、2.441和2.703,P均<0.05)。在首针免疫7、14和28 d后,3组的特异性IFN-γ的效应T细胞数比较差异有统计学意义(F=25.360、36.990和660.400,P均<0.01),CpG+铝佐剂疫苗组分别为179.68±69.26、395.58±139.64、563.50±43.79,均高于铝佐剂疫苗组(t=3.969、5.292和22.310,P均<0.01)。结论CpG1826能和铝佐剂协同增强大肠埃希菌表达的SARS-CoV-2亚单位疫苗诱导的体液及细胞免疫应答水平,显著提高其免疫原性,具有较强的临床意义。Objective To evaluate the synergistic effect of CpG1826 and aluminum adjuvant on the immunogenicity of SARS-CoV-2 subunit vaccine expressed in Escherichia coli.Methods Escherichia coli was used to efficiently express SARS-CoV-2 subunit antigen.CpG1826 and aluminum adjuvant were added after purification.BALB/c mice were divided into three groups including aluminum adjuvant vaccine group,CpG+aluminum adjuvant vaccine group and blank group with 18 mice in each group,and were injected at day 0,7 and 14 intraperitoneally.Blood and spleen were collected at day 7,14 and 28 after the first immunization to detect the serum IgG,neutralizing antibody,and IFN-γcytokine level in the supernatant of mouse spleen cells.Results At day 28 after primary immunity,the levels of IgG,the inhibition rates of binding antibody and the levels of neutralizing antibody in three groups were significantly different(F=21.440,159.400 and 8.470,P all<0.05);and in CpG+aluminum adjuvant vaccine group were 6.91±0.20,(91.01±4.60)%and 65.33±51.70,which were much higher than those in aluminum adjuvant vaccine group(t=2.892,2.441 and 2.703,P all<0.05).At day 7,14 and 28 after initial immunity,the numbers of specific IFN-γeffector T cells in three groups were significantly different(F=25.360,36.990 and 660.400,P all<0.01);and in CpG+aluminum adjuvant vaccine group were 179.68±69.26,395.58±139.64,563.50±43.79,which were all much higher than those in aluminum adjuvant vaccine group(t=3.969,5.292 and 22.310,P all<0.01).Conclusions CpG1826 and aluminum adjuvant can synergistically enhance the level of humoral and cellular immune response induced by the SARS-CoV-2 subunit vaccine expressed in Escherichia coli,and improve the immunogenicity significantly,which have great clinical significance.

关 键 词：新型冠状病毒 CpG1826 重组亚单位疫苗 免疫保护 

分 类 号：R392-33[医药卫生—免疫学]