不同佐剂配伍的新型冠状病毒和流感病毒联合疫苗在小鼠中的免疫原性评价  

Immunogenicity evaluation of SARS-CoV-2 and influenza virus combined vaccine formulated with different adjuvants in mice

作　　者：杨洁 杨东升 吴杰 林凤杰 王文辉 杨安纳 庞德钦 戴旱雨 孟胜利 郭靖 王泽鋆 申硕 Yang Jie;Yang Dongsheng;Wu Jie;Lin Fengjie;Wang Wenhui;Yang Anna;Pang Deqin;Dai Hanyu;Meng Shengli;Guo Jing;Wang Zejun;Shen Shuo Wuhan(Institute of Biological Products Co.,Ltd.,National Engineering Technology Research Center for Combined Vaccines,National Key Laboratory for Novel Vaccines Research and Development of Emerging Infectious Diseases,Hubei Province Vaccine Technology Innovation Center,Wuhan 430207,China)

机构地区：[1]武汉生物制品研究所有限责任公司,国家联合疫苗工程技术研究中心,新突发传染病新型疫苗研发全国重点实验室,湖北省疫苗技术创新中心,武汉430207

出　　处：《国际生物制品学杂志》2025年第1期1-9,共9页International Journal of Biologicals

基　　金：国家重点研发计划(2020YFC0842100);湖北省科技重大专项(2021ACB005)。

摘　　要：目的评价分别用Al(OH)3、MF59、AS03和QS21佐剂配伍的新型冠状病毒(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)和流感病毒联合疫苗在小鼠中的免疫原性。方法分别用Al(OH)3、MF59、AS03和QS21佐剂配制SARS-CoV-2(灭活)和四价流感病毒(裂解)联合疫苗,在第0、14天分别腹腔注射免疫BALB/c小鼠,第14、28天采血检测血清抗SARS-CoV-2抗体滴度和流感血凝抑制滴度,并在第28天分离脾脏淋巴细胞检测针对SARS-CoV-2和流感病毒的细胞免疫应答。结果不同佐剂的SARS-CoV-2和流感病毒联合疫苗均能诱导小鼠产生抗原特异性的抗体和细胞免疫应答。初次免疫后28 d,MF59佐剂组诱导了较高的抗SARS-CoV-2结合抗体和中和抗体,几何平均滴度(geometric mean titer,GMT)分别为89144和5418;MF59佐剂组也诱导了较高的针对四价流感病毒(H1N1、H3N2、BV、BY)的血凝抑制抗体,GMT分别为4457、5120、1470和5881;MF59和AS03佐剂组诱导了较强的针对SARS-CoV-2的Th1型(IFN-γ、IL-2)细胞免疫应答,与正常对照组的斑点形成单位差异均有统计学意义(IFN-γ:H=16.69,P<0.01;IL-2:H=15.21,P<0.05);AS03佐剂组诱导了较强的针对H1N1、H3N2、BV、BY流感病毒的Th1型(IFN-γ、IL-2)细胞免疫应答,与正常对照组的斑点形成单位差异均有统计学意义(IFN-γ:H=12.93、12.17、11.82、13.61,P<0.05;IL-2:H=12.24、12.42、11.72、12.43,P<0.05)。结论不同佐剂配方的SARS-CoV-2和流感病毒联合疫苗的免疫原性及抗原特异性抗体和细胞免疫应答均不同,证明了联合疫苗配方研究中佐剂的重要性。Objective To evaluate the immunogenicity of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and influenza virus combined vaccine formulated with 4 adjuvants Al(OH)3,MF59,AS03 and QS21 in mice.Methods Adjuvants Al(OH)3,MF59,AS03 and QS21 were used respectively to prepare SARS-CoV-2(inactivated)and tetravalent influenza virus(split)combined vaccine.BALB/c mice were immunized by intraperitoneal injection on day 0(D0)and D14,respectively.Blood samples were collected on D14 and D28 to detect antibody titers against SARS-CoV-2 and hemagglutination inhibition titers of influenza.Spleen lymphocytes were isolated on D28 to detect cellular immune responses to both SARS-CoV-2 and influenza virus.Results SARS-CoV-2 and influenza virus combined vaccine with different adjuvants induced both antigen-specific antibody responses and cellular immune responses in mice.At D28 post-initial immunization,MF59 adjuvant group induced high levels of SARS-CoV-2 binding antibodies and neutralizing antibodies,with geometric mean titers(GMTs)of 89144 and 5418,respectively,and MF59 group also induced high levels of hemagglutination-inhibiting antibodies against the quadrivalent influenza virus strains(H1N1,H3N2,BV,BY),with GMTs of 4457,5120,1470 and 5881,respectively.Both the MF59 and AS03 groups induced robust Th1-type(IFN-γ,IL-2)cellular immune responses against SARS-CoV-2,with spot forming units(SFUs)statistically significantly higher than those of Mock group(IFN-γ:H=16.69,P<0.01;IL-2:H=15.21,P<0.05).The AS03 group induced a strong Th1-type(IFN-γ,IL-2)cellular immune response against the quadrivalent influenza virus strains(H1N1,H3N2,BV,BY),with SFUs statistically significantly higher than those of Mock group(IFN-γ:H=12.93,12.17,11.82,13.61,P<0.05;IL-2:H=12.24,12.42,11.72,12.43,P<0.05).Conclusion The immunogenicity as well as specific antibody and cellular immune responses of SARSCoV-2 and influenza virus combined vaccine with different adjuvant formulations are different,indicating the importance of adjuvants in the developm

关 键 词：新型冠状病毒 流感病毒 联合疫苗 佐剂 体液免疫 细胞免疫 

分 类 号：R392[医药卫生—免疫学]