H5N1DNA疫苗与重组痘苗病毒疫苗在小鼠中不同联合免疫方案对免疫原性的影响  

Effects of various prime-boost regimes on immunities in mice by using DNA and reocmbinant vaccinia-based H5N1 vaccines

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

机构地区：[1]中国疾病预防控制中心病毒病预防控制所、卫生部医学病毒学重点实验室,北京102206

出　　处：《中华微生物学和免疫学杂志》2014年第9期668-672,共5页Chinese Journal of Microbiology and Immunology

基　　金：传染病重大专项（2013ZX10004001-004）;国家科技支撑计划项目（2006BAD06A15）

摘　　要：目的：本研究旨在优化人高致病性禽流感病毒H5N1重组DNA疫苗与重组痘苗病毒疫苗联合应用的免疫方案。方法我们将前期制备的含H5N1（安徽株）结构基因的两种重组DNA疫苗（分别基于pVRC与pIRES载体骨架）及一种重组痘苗病毒（天坛株）疫苗，采用不同初免方式联合免疫BALB/c小鼠，比较分析抗原特异的体液[血凝素（hemagglutinin，HA）抑制抗体（HAI）、神经氨酸酶（neuraminidase，NA）特异性抗体、中和抗体]与细胞免疫应答（IFN-γELISPOT）特点。结果H5N1重组DNA疫苗初免、H5N1重组痘苗病毒疫苗加强的联合免疫可激发较强的体液与细胞免疫应答；其中H5N1重组DNA疫苗皮内电转初免组比肌肉电转初免组诱导的中和抗体更高。此外，基于pVRC载体的H5N1重组DNA疫苗初免诱导的HAI抗体及NA特异的细胞免疫均高于基于pIRES载体的DNA疫苗初免组；基于pVRC载体的H5N1重组DNA疫苗肌肉注射电转初免组诱导的HA特异的细胞免疫亦高于基于pIRES载体的H5N1重组DNA疫苗。结论各组H5N1重组DNA疫苗与重组痘苗病毒疫苗联合应用可诱导多个抗原特异的体液与细胞免疫应答，不同联合免疫方案对免疫原性的影响显著。该研究为新型H5N1疫苗的研发及免疫方案的优化应用奠定了基础。Objective To develop an effective and broad immune protective vaccination strategy by using DNA and recombinant vaccinia-based H5N1 vaccines.Methods BALB/c mice were immunized with various prime-boost regimens by using different DNA （ pIRES-based or pVRC-based） and recombinant vaccinia （Tiantan strain, rTTV）-based H5N1 vaccines expressing multivalent antigens （HA, NA, M1 and M2）.The differences of immunity induced by two DNA vaccines were compared between intradermal electro -poration （IDE） and intramuscular electroporation （IME） deliveries.Immune responses were analyzed by hemagglutination inhibition（ HAI） assay, neuraminidase （ NA）-specific antibody measured by ELISA , mi-croneutralization assay and IFN-γELISPOT assay .Results High levels of humoral immunity and T cell re -sponses were induced in mice primed with DNA-based vaccine than those primed with rTTVb-ased vaccine . DNA priming by IDE resulted in higher levels of neutralizing antibody in mice than those by IME delivery . Higher levels of HAI and anti-NA antibodies as well as NA-specific T cell responses were induced by pVRC-based DNA prime than those by pIRES-based DNA prime .HA-specific T cell responses were also enhanced in mice primed with pVRC-based DNA than those primed with pIRES-based DNA by IME .Conclusion The prime-boost strategies by using DNA-based vaccine in combination with rTTV-based H5N1 vaccine could induce humoral and T cell responses in mice against multi-antigens .Immunities induced by vaccines in com-bination might be modulated by various prime regimes .The study provided references for the further develop-ment of novel H5N1 vaccine and the optimization of immunization programs of combined multi-antigen vac-cine 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)载体疫苗 联合免疫 

分 类 号：R392[医药卫生—免疫学]