M2e合成肽流感通用疫苗的研究  

DEVELOPMENT OF M2E BASED SYNTHETIC PEPTIDE AS UNIVERSAL INFLUENZA VACCINE

作　　者：杨馥如[1] 于海[1] 马继红[1] 周艳君[1] 童光志[1] 

机构地区：[1]中国农业科学院上海兽医研究所,上海200241

出　　处：《中国动物传染病学报》2013年第1期1-7,共7页Chinese Journal of Animal Infectious Diseases

基　　金：国家科技支撑计划重点项目(2010BAD04B03);国家国际科技合作项目"重大动物源性人兽共患病预防与控制的关键技术;中央级公益性科研院所基本科研业务费项目(2010JB01);上海市科委基础研究重点项目(10JC1417300)

摘　　要：M2蛋白是甲型流感病毒的跨膜蛋白,其优点为不易变异,且N端24个氨基酸组成的胞外区(M2e)十分保守,适合作为通用流感疫苗的靶标。因此本实验将4个拷贝的M2e通过赖氨酸与通用Th细胞表位偶联获得M2e分支肽(M2e-MAP),添加弗氏佐剂制备成合成肽疫苗免疫小鼠,评价其免疫原性及异源攻毒保护效力。ELISA实验结果表明,该疫苗能刺激机体产生高水平的抗M2e特异性IgG抗体;细胞因子IL-4的检测进一步说明了其能诱导产生高的体液免疫应答水平,ELISPOT实验从IL-4和IFN-γ两个方面分别说明了该疫苗不仅可以诱导高的体液免疫应答,而且能刺激机体产生高水平的细胞免疫应答。对免疫小鼠攻H9N2,通过肺病毒分离滴定和肺组织病理切片等方法检测攻毒保护效果,结果均表明,M2e分支肽疫苗能对异源病毒的攻击产生较好的保护效力。上述结果为流感通用疫苗的研究提供了一种参考思路。Matrix protein 2 （M2） is a transmembrane protein of influenza type A virus and shows remarkable stability during viral evolution. The N-terminal extracellular-domain containing 24 aa is highly conserved among influenza A virus strains and thus considered as a target for designing universal influenza vaccines. In the present study, we designed a tetra-branched multiple antigenic peptide （MAP） based vaccine （M2e-MAP）, each peptide containing four copies of M2e and one copy ofT helper （Th） cell epitope. Mice were vaccinated with M2e-MAP emulsified in Freund＇s adjuvant and blood samples were taken for testing of immune responses. The peptide vaccine induced strong M2e-specific IgG antibody response as determined in ELISA. The testing of IL-4 further demonstrated its capability of inducing high-level humoral immune response. The ELISPOT of IL-4 and IFN-γ also showed that M2e-MAP stimulated high cellular immune response. Then, mice were challenged with a heterologous H9N2 virus and protective efficiency was evaluated based on virus isolation and lung histopathological examination. Strong protection was observed in mice vaccinated with M2e-MAP. This study provided useful information for further development of a universal influenza vaccine.

关 键 词：M2e 通用疫苗 免疫交叉保护 

分 类 号：S852.5[农业科学—基础兽医学]