Animal Health Biotechnology, Temasek Life Sciences Laboratory, Singapore, Singapore.
Animal Health Biotechnology, Temasek Life Sciences Laboratory, Singapore, Singapore; Department of Microbiology Faculty of Medicine, National University of Singapore, Singapore, Singapore.
Antiviral Res. 2014 May;105:143-51. doi: 10.1016/j.antiviral.2014.03.002. Epub 2014 Mar 15.
H5N1 HPAI virus continues to be a severe threat for public health, as well as for the poultry industry, due to its high mortality and antigenic drift rate. There is no monovalent vaccine available which provides broad protection against those major circulating strains. In the present study, a monovalent H5 vaccine strain was developed with antigenic sequence analysis and epitope mutations. H5 from Indonesia strain (A/Indonesia/CDC669/2006) was used as backbone sequence. Three amino acids were mutated to express immunogenic epitopes from other circulating H5N1s in the backbone. RG influenza virus expressing the epitope-chimeric H5 can react in HI with multiple H5 monoclonal antibodies which fail to neutralize wild type CDC669. High titers in HI and virus neutralization against different clades H5N1s (clade 1, 2, 4 and 7) were detected using sera from mice immunized with the epitope-chimeric H5N1. The monovalent vaccine with RG-epitope-chimeric H5N1 protected mice from lethal challenge with H5N1s of different clades, including clade 1.0, 2.1, 2.2 and 2.3. This study indicates that the broad immune response elicited by this single H5N1 virus allows it to be a promising candidate for a monovalent H5 universal vaccine.
H5N1 高致病性禽流感病毒由于其高死亡率和抗原漂移率，仍然对公共卫生和家禽业构成严重威胁。目前还没有单价疫苗能够提供针对这些主要流行株的广泛保护。在本研究中，通过抗原序列分析和表位突变开发了一种单价 H5 疫苗株。印度尼西亚株（A/Indonesia/CDC669/2006）的 H5 被用作骨架序列。突变了三个氨基酸，以在骨架中表达来自其他循环 H5N1 的免疫原性表位。表达表位嵌合 H5 的 RG 流感病毒可以与不能中和野生型 CDC669 的多种 H5 单克隆抗体发生 HI 反应。用免疫嵌合 H5N1 的表位的 RG-嵌合 H5N1 的血清检测到针对不同 H5N1 （1 类、2 类、4 类和 7 类）的 HI 和病毒中和的高滴度。用 RG-嵌合 H5N1 单价疫苗免疫的小鼠可以抵抗不同 H5N1 （包括 1.0 类、2.1 类、2.2 类和 2.3 类）的致死性挑战。这项研究表明，这种单一 H5N1 病毒引起的广泛免疫反应使其成为单价 H5 通用疫苗的有前途的候选者。
