新型冠状病毒mRNA疫苗与重组蛋白疫苗混合免疫在小鼠体内的免疫原性  

Immunogenicity of mixture of SARS-CoV-2 mRNA vaccine and recombinant protein vaccine in mice

作　　者：张怡 张佳璐 程飞冉[2] 张旋旋 梁争论 毛群颖[2] 李秀玲[1] 贺倩 ZHANG Yi;ZHANG Jialu;CHENG Feiran;ZHANG Xuanxuan;LIANG Zhenglun;MAO Qunying;LI Xiuling;HE Qian(Shanghai Institute of Biological Products Co.,Ltd.,State Key Laboratory of Novel Vaccines for Emerging Infectious Diseases,Shanghai 200051,China;不详)

机构地区：[1]上海生物制品研究所有限责任公司新突发传染病新型疫苗研发全国重点实验室,上海200051 [2]中国食品药品检定研究院,国家卫生健康委员会生物技术产品检定方法及其标准化重点实验室,国家药品监督管理局生物制品质量研究与评价重点实验室,北京102629 [3]吉林大学生命科学院艾滋病疫苗国家工程实验室,吉林长春130012

出　　处：《中国生物制品学杂志》2024年第12期1409-1414,共6页Chinese Journal of Biologicals

基　　金：中国医学科学院医学与健康科技创新工程(2021-I2M-5-005);中国医学科学院中央级公益性科研院所基本科研业务费专项资金(2023-PT350-01)。

摘　　要：目的 评价新型冠状病毒脂质纳米颗粒包裹的mRNA疫苗(mRNA-LNP)与重组蛋白-铝佐剂疫苗(PS-Alum)混合免疫在小鼠体内的免疫原性,为不同技术路线疫苗联合免疫提供实验数据。方法 以mRNA-LNP和PS-Alum疫苗为研究对象,比较疫苗单独免疫及联合免疫雌性BALB/c小鼠的免疫应答水平。联合免疫策略分别为双侧免疫(bilateral)和混合免疫(mix),bilateral组在小鼠一侧胫骨前肌免疫mRNA-LNP疫苗,另一侧胫骨前肌免疫等体积PSAlum疫苗,mix组将mRNA-LNP与PS-Alum疫苗等体积混合后,分别接种小鼠两侧胫骨前肌;免疫1和2针后检测抗体反应,与单独免疫mRNA-LNP疫苗进行比较,评价混合疫苗的免疫效果。将mRNA-LNP与PS-Alum疫苗等体积混合,体外4℃放置0、48 h及7、14、35 d后免疫雌性BALB/c小鼠,检测抗体应答和细胞免疫应答,初步评价混合疫苗的稳定性。结果 mix组小鼠血清IgG结合抗体几何平均滴度(geometric mean titer,GMT)在初免后第14天和加强免疫后第14天均高于mRNA、bilateral组(14 d:P分别为<0.000 1和0.243 9;35 d:P均<0.000 1);将混合疫苗体外4℃放置0、48 h及7、14、35 d后免疫小鼠,初免后放置48 h,小鼠血清IgG结合抗体GMT比0 h略有提升(P=0.017 7),随着放置时间延长,结合抗体GMT保持稳定;加强免疫后,相比0 h,随着放置时间延长,疫苗诱导的结合抗体、假病毒中和抗体和T细胞反应均未降低(P=0.421 1~0.999 9)。结论 制备mRNA-LNP与PS-Alum混合疫苗进行免疫,相比单独免疫可有效提升免疫原性,且混合疫苗在体外4℃放置35 d内免疫原性保持稳定。Objective To evaluate the immunogenicity of the mixture of lipid nanoparticle-encapsulated mRNA vaccine(mRNA-LNP)and aluminum adjuvanted protein subunit vaccine(PS-Alum)against SARS-CoV-2 in mice,and then to provide experimental data for the heterologous immunization strategy of different technology platforms.Methods Immune responses of mRNA-LNP and PS-Alum vaccines were compared in female BALB/c mice immunized with mRNA-LNP vaccine or PS-Alum vaccine alone,or in combination.The heterologous immunization strategies were bilateral immunization(bilateral)and mixed immunization(mix).In the bilateral group,the mice were immunized with mRNA-LNP vaccine in one side of the tibialis anterior muscle and with an equal volume of PS-Alum vaccine in the other.In the mix group,the mRNALNP and PS-Alum vaccines were mixed in equal volumes and administered separately to both sides of the tibialis anterior muscles of the mice.Antibody responses were detected after the primary and booster immunizations,and compared with those induced by mRNA-LNP alone to evaluate the immunogenic effect of the mixed vaccine.Additionally,the mRNA-LNP and PS-Alum vaccines were mixed in equal volumes and stored at 4℃for 0,48 h,as well as 7,14,and 35 d,respectively,before immunizing female BALB/c mice.The antibody response and cellular immune response were then measured to preliminarily assess the stability of the mixed vaccine.Results The geometric mean titer(GMT)of RBD specific serum binding IgG of mice in the mix group was higher than that in the mRNA and bilateral groups 14 d after both the primary immunization and booster immunization(14 d:P<0.0001 and 0.2439,respectively;35 d:each P<0.0001).When the mixed vaccine was stored at 4℃ in vitro for 0,48 h,and 7,14,and 35 d before immunizing the mice,the GMT of serum binding IgG slightly increased 48 h after the primary immunization compared to 0 h(P=0.0177).As the storage time extended,the GMT of binding antibodies remained stable.After the booster immunization,compared to 0 h,the vaccine-induced bi

关 键 词：mRNA疫苗 重组蛋白疫苗 混合免疫 免疫策略 新型冠状病毒 

分 类 号：R183.3[医药卫生—流行病学]