重组甲基转移酶致弱水疱性口炎病毒的致病性与免疫原性

Pathogenicity and immunogenicity of recombinant methyltransferase-defective vesicular stomatitis virus

为了研究有效的水疱性口炎病毒疫苗,控制水疱性口炎疾病的蔓延,用甲基化能力致弱的重组水疱性口炎病毒VSV-E1764A,VSV-S1827A,VSV-Y1650A和VSV-F1691A作为疫苗,通过口腔灌服途径将1×106PFU的重组病毒接种5周龄BALB/c小鼠,研究以上重组病毒的致病性和免疫原性.结果表明:重组病毒VSV-S1827A,VSV-Y1650A和VSV-F1691A对小鼠的致病性减弱,而VSV-E1764A仍然具有较强的致病性;免疫后的小鼠用野生型水疱性口炎病毒(VSV)进行攻毒,发现VSV-S1827A和VSV-Y1650A能够诱导高水平的中和抗体,从而保护小鼠免于攻击.总之,甲基化酶致弱的水疱性口炎病毒VSV-S1827A和VSV-Y1650A不仅对动物的致病性减弱,而且表现出良好的免疫原性;因此,甲基化酶致弱的水疱性口炎病毒可能成为有良好开发前景的活疫苗.

To prevent the vesicular stomatitis virus（VSV） disease, using a panel of recombinant VSV（E1764A,S1827A,Y1650A,and F1691A） that were defective in mRNA cap methylation as vaccine to inoculate five-week-old BALB/c female mice through oral route with 1×106 PFU,the pathogenicity and immunogenicity of these viruses were determined.The result showed that recombinant S1827A,Y1650A,F1691A were attenuated in mice and E1764A was still pathogenic to mice.The immunized mice were challenged with wild type VSV.Mice immunized with S1827A and Y1650A trigged a high level of neutralizing antibody and were protected from virulent challenge.Taken together,the results above demonstrated that methyltransferase（MTase）-defective VSV（S1827A and Y1650A） were not only attenuated in animals,but also exhibited excellent immunogenicity.Therefore,MTase-defective viruses will be good live vaccine candidates against VSV.