Chimeric dengue type 2 (vaccine strain PDK-53)/dengue type 1 virus as a potential candidate dengue type 1 virus vaccine
Chimeric dengue type 2 (vaccine strain PDK-53)/dengue type 1 virus as a potential candidate dengue type 1 virus vaccine
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DOI：
10.1128/jvi.74.7.3020-3028.2000
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发表时间：
2000-04-01
影响因子：
5.4
通讯作者：
Kinney, RM
中科院分区：
文献类型：
--
作者：
Huang, CYH;Butrapet, S;Kinney, RM
我们构建了2型/1型嵌合登革病毒，含有DEN-2 16681病毒或其疫苗衍生物菌株PDK-53的非结构基因和结构基因的DEN-2/DEN-1病毒（编码衣壳蛋白、前膜蛋白和包膜糖蛋白）或其疫苗衍生物，菌株PDK-13，我们以前报道过DEN-2 PDK-53病毒的减毒标记由位于PDK-53病毒基因组结构基因区之外的遗传位点编码。含有DEN-2 PDK-53病毒的非结构基因和亲本DEN-116007病毒的结构基因的嵌合病毒保留了LLC-MK2细胞中小噬斑尺寸和温度敏感性的减毒标志物，在C6/36细胞中较低效率的复制，以及小鼠的减毒。这些嵌合病毒引起的针对DEN-I病毒的小鼠中和抗体滴度高于候选DEN-I PDK-13疫苗病毒或含有PDK-13病毒的结构基因的嵌合DEN-2/DEN-1病毒。DEN-I PDK-13病毒包膜蛋白突变影响小鼠体外表型和免疫原性。目前的PDK-13疫苗是人体试验中四种Mahidol候选DEN病毒疫苗中效率最低的。DEN-2/DEN-1嵌合病毒有可能成为DEN-1病毒疫苗的候选者。本研究表明，来自候选DEN-2 PDK-53疫苗的感染性克隆是用于开发嵌合黄病毒疫苗的有希望的减毒载体。
We constructed chimeric dengue type 2/type 1 (DEN-2/DEN-1) viruses containing the nonstructural genes of DEN-2 16681 virus or its vaccine derivative, strain PDK-53, and the structural genes (encoding capsid protein, premembrane protein, and envelope glycoprotein) of DEN-I 16007 virus or its vaccine derivative, strain PDK-13, We previously reported that attenuation markers of DEN-2 PDK-53 virus were encoded by genetic loci located outside the structural gene region of the PDK-53 virus genome. Chimeric viruses containing the nonstructural genes of DEN-2 PDK-53 virus and the structural genes of the parental DEN-1 16007 virus retained the attenuation markers of small plaque size and temperature sensitivity in LLC-MK2 cells, less efficient replication in C6/36 cells, and attenuation for mice. These chimeric viruses elicited higher mouse neutralizing antibody titers against DEN-I virus than did the candidate DEN-I PDK-13 vaccine virus or chimeric DEN-2/DEN-1 viruses containing the structural genes of the PDK-13 virus. Mutations in the envelope protein of DEN-I PDK-13 virus affected in vitro phenotype and immunogenicity in mice. The current PDK-13 vaccine is the least efficient of the four Mahidol candidate DEN virus vaccines in human trials. The chimeric DEN-2/DEN-1 virus might be a potential DEN-1 virus vaccine candidate. This study indicated that the infectious clones derived from the candidate DEN-2 PDK-53 vaccine are promising attenuated vectors for development of chimeric flavivirus vaccines.