乙脑/寨卡嵌合病毒株的生物学特性及免疫原性鉴定  

Biological characteristics and immunogenicity identification of Japanese encephalitis/Zika Chimeric virus strain

作　　者：黄荣 冷生玲 冯亚岚[1] 唐丽萍[1] 袁磊 杨健[1] HUANG Rong;LENG Sheng-ling;FENG Ya-lan;TANG Li-ping;YUAN Lei;YANG Jian(Basic Medicine and Forensics School,North Sichuan Medical College,Nanchong 637000;Department of Infectious Disease,Mianyang Central Hospital,Mianyang 621000,Sichuan China)

机构地区：[1]川北医学院基础医学与法医学院,四川南充637000 [2]绵阳市中心医院感染科,四川绵阳621000

出　　处：《川北医学院学报》2022年第8期969-973,共5页Journal of North Sichuan Medical College

基　　金：四川省南充市川北医学院市校合作项目(No.20SXQT0338;No.18SXHZ0495)。

摘　　要：目的:鉴定以乙脑病毒(JEV)疫苗株SA14-14-2为骨架的乙脑/寨卡(ZIKV)嵌合病毒,分析其作为疫苗候选株的可行性。方法:通过对嵌合病毒的噬斑形态鉴定和生长特性鉴定,初步判断嵌合病毒的毒力,并用嵌合病毒接种昆明鼠,检测其脑内、皮下及腹腔神经毒力,使用噬斑减少中和试验(PRNT)及免疫攻击试验分析嵌合病毒的免疫原性及免疫保护作用。结果:嵌合病毒比乙脑疫苗株SA14-14-2具有更小的噬斑;用不同的感染复数(0.1、0.01、0.001)感染BHK21细胞,可得到相似的生长曲线,复制速度较SA14-14-2慢,峰值出现较SA14-14-2晚;对昆明鼠有较强的神经毒力但无明显神经侵袭力;可诱导小鼠产生较高的中和抗体效价;能保护小鼠免受病毒自身脑内攻击并呈现典型的剂量效应;能与SA14-14-2产生一定程度的交叉反应。结论:嵌合病毒JE/ZIKA免疫原性良好,但对小鼠有较强的脑内神经毒力,嵌合病毒和乙脑疫苗株也有一定的交叉免疫。Objective:To identify the Japanese encephalitis/Zika chimeric virus(JE/ZIKV)based on Japanese encephalitis virus(JEV)vaccine strain SA14-14-2,and analyze its feasibility as a vaccine candidate strain.Methods:The growth characteristics of the chimeric virus were identified by the plaque assay,of which the neurotoxicity in the brain,subcutaneous and abdominal cavity were evaluated with Kunming mice.The immunogenicity and immune protection of chimeric virus were analyzed by plaque reduction neutralization test(PRNT)and immune attack test.Results:The plaque of JE/ZIKA virus was smaller than that produced by JEV SA14-14-2.BHK21 cells were infected with different multiplicity of infection(m.o.i was 0.1,0.01,and 0.001)got similar growth curve,while the peak appears later than those of strain SA14-14-2.No neuroinvasiveness but strong neurotoxicity were observed in Kunming mice.High neutralizing antibody titer was induced in mice,which could be able to protect mice from the chimeric virus brain attack and present a typical dose effect,and there was cross immunity with SA14-14-2.Conclusion:The chimeric JE/ZIKA virus showed good immunogenicity but has strong neurotoxicity in mice,and there is cross immunity between chimeric virus JE/ZIKA and Japanese encephalitis vaccine strain SA14-14-2.

关 键 词：乙脑病毒 寨卡病毒 嵌合病毒 免疫原性 免疫保护 

分 类 号：R373.3[医药卫生—病原生物学]