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首页> 外文期刊>The American Journal of Tropical Medicine and Hygiene >Genetically modified, live attenuated dengue virus type 3 vaccine candidates.
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Genetically modified, live attenuated dengue virus type 3 vaccine candidates.

机译：转基因的减毒活3型登革热病毒候选疫苗。

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摘要

Three novel recombinant dengue type 3 (DEN3) virus vaccine candidates have been generated from a DEN3 virus isolated from a mild outbreak of dengue fever in the Sleman area of central Java in Indonesia in 1978. Antigenic chimeric viruses were prepared by replacing the membrane precursor and envelope (ME) proteins of recombinant DEN4 (rDEN4) virus with those from DEN3 Sleman/78 in the presence (rDEN3/4Delta30(ME)) and the absence (rDEN3/4(ME)) of the Delta30 mutation, a previously described 30-nucleotide deletion in the 3' untranslated region. In addition, a full-length infectious cDNA clone was generated from the DEN3 isolate and used to produce rDEN3 virus and the vaccine candidate rDEN3Delta30. The chimeric viruses rDEN3/4(ME) and rDEN3/4Delta30(ME) appear to be acceptable vaccine candidates since they were restricted in replication in severe combined immune deficiency mice transplanted with human hepatoma cells, in rhesus monkeys, and in Aedes and Toxorynchites mosquitoes, and each was protective inrhesus monkeys against DEN3 virus challenge. The rDEN3/4(ME) and rDEN3/4Delta30(ME) viruses were comparable in all parameters evaluated, indicating that antigenic chimerization resulted in the observed high level of attenuation. Surprisingly, rDEN3Delta30 was not attenuated in any model tested when compared with wild-type rDEN3 and therefore, is not a vaccine candidate at present. Thus, the rDEN3/4(ME) and rDEN3/4Delta30(ME) antigenic chimeric viruses can be considered for evaluation in humans and for inclusion in a tetravalent dengue vaccine.
机译：从1978年从印度尼西亚中爪哇省Sleman地区的一次轻度登革热暴发中分离出的DEN3病毒产生了三种新型的重组登革热3型（DEN3）疫苗候选物。通过替换膜前体和重组DEN4（rDEN4）病毒的包膜（ME）蛋白与DEN3 Sleman / 78的蛋白在存在（rDEN3 / 4Delta30（ME））和不存在（rDEN3 / 4（ME））的情况下，都存在Delta30突变，如前所述30 -在3'非翻译区中的-核苷酸缺失。另外，从DEN3分离株产生全长感染性cDNA克隆，并用于产生rDEN3病毒和候选疫苗rDEN3Delta30。嵌合病毒rDEN3 / 4（ME）和rDEN3 / 4Delta30（ME）似乎是可以接受的候选疫苗，因为它们在移植有人肝癌细胞的重度联合免疫缺陷小鼠，恒河猴，伊蚊和弓形虫蚊子的复制中受到限制，并且每只都是保护性的猕猴抵抗DEN3病毒攻击。 rDEN3 / 4（ME）和rDEN3 / 4Delta30（ME）病毒在所有评估参数中均具有可比性，表明抗原嵌合化导致观察到的高水平减毒。令人惊讶的是，与野生型rDEN3相比，rDEN3Delta30在任何测试的模型中均未减毒，因此目前不是候选疫苗。因此，可以考虑将rDEN3 / 4（ME）和rDEN3 / 4Delta30（ME）抗原性嵌合病毒用于人体评估和纳入四价登革热疫苗。

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