Deshmukh Tejaswini M, Lole Kavita S, Tripathy Anuradha S, Arankalle Vidya A
Hepatitis Division, National Institute of Virology, Microbiological Containment Complex, Sus Road, Pashan, Pune 411021, India.
Vaccine. 2007 May 30;25(22):4350-60. doi: 10.1016/j.vaccine.2007.03.040. Epub 2007 Apr 9.
Hepatitis E virus (HEV) is a major cause of enterically transmitted acute hepatitis of adults in developing nations. Our present studies show that, the complete ORF2 gene (1-660 amino acids, a.a.) coding for capsid protein of HEV as candidate DNA vaccine induced significant specific humoral and cellular immune responses in mice. Gene gun based DNA administration led to higher seroconversion rates and HEV-specific antibody titers as against needle-injection method. The region (458-607a.a.) within ORF2 protein is reported to harbour the predominant neutralization epitope/s (NE) of HEV. The NE DNA also induced HEV-specific immune responses in mice. NE-based DNA-prime-protein boost approach was observed to be superior to NE DNA based approach. Co-administration of plasmid expressing mouse granulocyte macrophage colony stimulating factor (GM-CSF) induced immune response at similar level as that with ORF2/NE plasmid alone. IgG1 was the predominant isotype irrespective of the approach used. HEV-specific antibodies in seroconverted mice sera could bind/neutralize HEV in an in vitro ELISA-based assay. In conclusion, efficacy of ORF2 and NE based DNA/DNA-prime-protein-boost approaches are worth exploring in monkey model.
戊型肝炎病毒（HEV）是发展中国家成人肠道传播急性肝炎的主要病因。我们目前的研究表明，编码HEV衣壳蛋白的完整ORF2基因（1 - 660个氨基酸，a.a.）作为候选DNA疫苗在小鼠中诱导了显著的特异性体液免疫和细胞免疫反应。与注射法相比，基于基因枪的DNA给药导致更高的血清转化率和HEV特异性抗体滴度。据报道，ORF2蛋白内的区域（458 - 607a.a.）含有HEV的主要中和表位（NE）。NE DNA也在小鼠中诱导了HEV特异性免疫反应。观察到基于NE的DNA初免-蛋白加强方法优于基于NE DNA的方法。共注射表达小鼠粒细胞巨噬细胞集落刺激因子（GM - CSF）的质粒诱导的免疫反应与单独使用ORF2/NE质粒时相似。无论使用何种方法，IgG1都是主要的亚型。血清转化小鼠血清中的HEV特异性抗体可以在基于ELISA的体外试验中结合/中和HEV。总之，基于ORF2和NE的DNA/DNA初免-蛋白加强方法在猴模型中的疗效值得探索。
