含H5N1多个结构抗原的DNA疫苗与重组痘苗病毒疫苗联合免疫小鼠可明显增强免疫原性  

The Immunogenicity in Mice Enhanced Significantly via Prime-boost Vaccination with DNA-based or Recombinant Vaccinia(Tiantan) Viral-based H5N1 Vaccine Candidates Containing Multi-structural Antigens

作　　者：王文[1] 陈红[1] 邓瑶[1] 杨扬[1] 殷霄[1] 王敏[1] 周剑芳[1] 舒跃龙[1] 阮力[1] 谭文杰[1] 

机构地区：[1]中国疾病预防控制中心病毒基因工程重点实验室,病毒病预防控制所,北京102206

出　　处：《病毒学报》2011年第6期594-598,共5页Chinese Journal of Virology

基　　金：“十一五”国家科技支撑计划项目(2006BAD06A15);国家重点研究发展计划(973)项目(2005CB523000)

摘　　要：本研究旨在研发经济、高效的人高致病性禽流感病毒H5N1实验疫苗并优化免疫方案。利用本实验室前期构建的含有H5N1(安徽株)结构基因的多个单顺反子(HAop和NAop)和双顺反子(HAop/M2和NAop/M1)DNA疫苗及重组痘苗病毒(天坛株)疫苗,采用不同方案(单独或联合)免疫BALB/c小鼠,初步分析了抗原特异性体液免疫(HA血凝抑制抗体,NA特异性抗体,中和抗体及M1与M2特异性抗体)和细胞免疫应答(IFN-γELIS-pot)的特点。结果表明:DNA疫苗与重组痘苗病毒(天坛株)疫苗联合免疫可以激发较强的多个抗原特异的免疫应答,尤其是体液免疫应答,明显优于DNA疫苗或重组痘苗病毒(天坛株)疫苗单独免疫;联合免疫方案中DNA疫苗初免所激发的HA与NA特异的体液免疫应答强于重组痘苗病毒(天坛株)疫苗初免,然而M1与M2特异的体液免疫应答则反之。本研究为新型H5N1疫苗的研发及免疫方案的优化奠定了基础。This study aimed to develop an effective experimental vaccine against highly pathogenic HSN1 A- vian Influenza （HPAI） virus and to optimize their immunization programs. As reported previously, various DNA-based or recombinant vaccinia viral（Tiantan）-based HSN1 vaccine candidates, which containing a single cistronic construct （HAop, or NAop） or a bieistronic construct （HAop/M2 or NAop/M1） of HSN1 influenza virus （Anhui strain） were constructed and characterized in our lab. In this study, we further analysed the immunogenicity in mice of these vaccine candidates by various protocols （single or combined immunization）. Our results showed that., comparing with immunization with DNA-based or rTTV-based HSN1 vaccine only, combined DNA-based with rTTV-based HSN1 vaccine immunization via prime-boost strategy enhanced immune response significantly against multi-HSN1 antigens detected by hemagglutina- tion inhibition （HI） assay, NA- or M1- or M2-specific antibody detection, and micro-neutralizing antibody test and IFN-7 ELISpot assay. Priming with DNA-based vaccine induced higher level of humoral response against HA or NA antigen than priming with rTTV-based vaccine; In contract, M1 and M2-specific anti- body levels were higher among that of priming with rTTV -based vaccine. These findings provide a basis for further development of novel HSN1 vaccines and for the optimization of the immunization programs of combined multi-antigens vaccine candidates.

关 键 词：人高致病性禽流感病毒 H5N1 DNA疫苗 重组痘苗病毒(天坛株)疫苗 联合免疫 

分 类 号：R373.1[医药卫生—病原生物学] R373.9[医药卫生—基础医学]