Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics
Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics
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DOI：
10.1006/viro.2002.1742
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发表时间：
2003-01-05
期刊：
影响因子：
3.7
通讯作者：
Matsuoka, Y
中科院分区：
文献类型：
--
作者：
Subbarao, K;Chen, HL;Matsuoka, Y
类似一九九七年在香港感染人类的甲型禽流感H5 N1病毒继续在水禽身上传播，并在区内的家禽身上重新出现，令人担心这些病毒可能会在人类身上再次出现。目前许可的三价灭活流感疫苗含有来自流行毒株的血凝素（HA）和神经氨酸酶基因，其背景是来自疫苗供体毒株A/波多黎各/8/34（PR 8）的内部基因。这种候选疫苗病毒目前尚未被许可用于预防人类感染H5 N1流感病毒。通过基于质粒的反向遗传学产生转染的H5 N1/PR 8病毒。去除与鸡高致病性相关的HA基因中的多碱性氨基酸基序，以及H5 N1/PR 8转染病毒的新基因型，在不改变HA抗原性的情况下减毒了鸡和小鼠的病毒。从该病毒制备的福尔马林灭活疫苗具有免疫原性，并保护小鼠免受随后的野生型H5 N1病毒攻击。这是第一次成功地尝试开发一种H5 N1疫苗种子病毒，该病毒类似于目前获得许可的甲型流感疫苗中使用的病毒，其特性使其成为一种有希望的候选病毒，可用于人体进一步评估。(C)2002 Elsevier Science（美国）。
Avian influenza A H5N1 viruses similar to those that infected humans in Hong Kong in 1997 continue to circulate in waterfowl and have reemerged in poultry in the region, raising concerns that these viruses could reappear in humans. The currently licensed trivalent inactivated influenza vaccines contain hemagglutinin (HA) and neuraminidase genes from epidemic strains in a background of internal genes derived from the vaccine donor strain, A/Puerto Rico/8/34 (PR8). Such reassortant candidate vaccine viruses are currently not licensed for the prevention of human infections by H5N1 influenza viruses. A transfectant H5N1/PR8 virus was generated by plasmid-based reverse genetics. The removal of the multibasic amino acid motif in the HA gene associated with high pathogenicity in chickens, and the new genotype of the H5N1/PR8 transfectant virus, attenuated the virus for chickens and mice without altering the antigenicity of the HA. A Formalin-inactivated vaccine prepared from this virus was immunogenic and protected mice from subsequent wild-type H5N1 virus challenge. This is the first successful attempt to develop an H5N1 vaccine seed virus resembling those used in currently licensed influenza A vaccines with properties that make it a promising candidate for further evaluation in humans. (C) 2002 Elsevier Science (USA).