摘要
目的研究登革病毒(dengue virus,DENV)的多价DNA疫苗pVAX1-EDIII在小鼠体内的免疫原性及其保护作用。方法采用真核表达载体p VAX1,设计并构建含4种血清型登革病毒EDIII结构域的DNA疫苗。在第0、14和42天采用电脉冲肌肉导入方式免疫小鼠。末次免疫后1周,ELISA检测针对4种血清型登革病毒的血清特异性IgG抗体水平;ELISpot检测免疫后小鼠脾细胞分泌特异性IL-4、IFN-γ的水平;体内中和实验检测小鼠免疫后血清对感染DENV和寨卡病毒(Zika virus,ZIKV)乳鼠的保护效力。结果与对照组相比,电脉冲肌肉导入DNA疫苗诱导产生较高滴度的IgG抗体与较强的细胞免疫应答。免疫后血清对致死剂量DENV感染的3日龄乳鼠有完全保护作用,对ZIKV感染C57BL/c 1日龄乳鼠有部分保护作用。结论电脉冲肌肉导入登革DNA多价疫苗免疫可诱导针对4种血清型登革病毒的特异性体液免疫以及细胞免疫应答并能有效抵抗DENV的致死剂量攻毒,对ZIKV也能产生一定的保护效应,具有广谱抗黄病毒感染的潜力。
To explore the immunogenicity and protective effect of dengue virus(DENV)polyvalent DNA vaccine pVAX1-EDIII in mice,a DNA vaccine containing EDIII domains of four serotypes of dengue virus was designed and constructed using eukaryotic expression vector p VAX-1.The mice were immunized by intramuscular injection with electroporation on days 0,14 and 42.One week after the last immunization,the specific IgG antibody levels against the four serotypes of dengue virus were detected by ELISA.The levels of specific IL-4 and IFN-γsecreted by spleen cells of immunized mice were detected by ELISpot.In vivo neutralization assay was used to test the protective efficacy of serum from immunized mice against DENV and Zika virus(ZIKV)in suckling mice.Data showed that intramuscular injection with electroporation of tetravalent dengue DNA vaccine could induce specific humoral and cellular immune responses against four serotypes of dengue virus.The post-immunization serum can protect 3-day-old suckling mice from lethal DENV attack,indicating that the vaccine produces neutralizing antibodies sufficient to withstand lethal challenges,and the serum also has a partial protective effect against Zika virus and the potential of broad-spectrum anti-Flavivirus infection.
作者
周伃欣
何久香
全纹萱
赵镜
李晋涛
ZHOU Yuxin;HE Jiuxiang;QUAN Wenxuan;ZHAO Jing;LI Jintao(Department of Military Biosafety,College of Basic Medicine,Army Medical University,Chongqing 400038,China;School of Pharmacy and Bioengineering,Chongqing University of Technology,Chongqing 400054,China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2023年第1期70-77,共8页
Immunological Journal
基金
国家自然科学基金面上项目(81570497)。
关键词
登革病毒
DNA疫苗
电脉冲肌肉导入
免疫应答
寨卡病毒
Dengue virus
DNA vaccine
Intramuscular injection with electroporation
Immune response
Zika virus
