Synthetic Generation of Influenza Vaccine Viruses for Rapid Response to Pandemics
Synthetic Generation of Influenza Vaccine Viruses for Rapid Response to Pandemics
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DOI：
10.1126/scitranslmed.3006368
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发表时间：
2013-05-15
影响因子：
17.1
通讯作者：
Venter, J. Craig
中科院分区：
文献类型：
--
作者：
Dormitzer, Philip R.;Suphaphiphat, Pirada;Venter, J. Craig
在2009年H1N1流感大流行期间，该病毒的疫苗仅在人类感染达到峰值之后才大量使用。为了加速未来大流行的疫苗可用性，我们开发了一种合成方法，该方法从序列数据中非常迅速地产生了疫苗病毒。从血凝素（HA）和神经氨酸酶（Na）基因序列开始，我们将一种酶促的，无细胞的基因组装技术与酶促误差校正结合在一起，以允许快速，准确的基因合成。然后，我们使用这些合成的HA和Na基因来转染Madin-Darby犬肾（MDCK）细胞，这些细胞具有用于疫苗制造的，该疫苗用病毒RNA表达构建体编码HA和Na，以及编码病毒骨链基因的质粒DNA和质粒DNA。从这些MDCK细胞中拯救了用于疫苗的病毒。我们通过改进的疫苗病毒主链进行了救援，增加了必需疫苗抗原的产量，HA。合成疫苗种子的产生，再加上更有效的疫苗释放分析，将通过瞬时电子数据交换系统加速对流感大流感的反应，然后进行实时，地理分散的疫苗生产。
During the 2009 H1N1 influenza pandemic, vaccines for the virus became available in large quantities only after human infections peaked. To accelerate vaccine availability for future pandemics, we developed a synthetic approach that very rapidly generated vaccine viruses from sequence data. Beginning with hemagglutinin (HA) and neuraminidase (NA) gene sequences, we combined an enzymatic, cell-free gene assembly technique with enzymatic error correction to allow rapid, accurate gene synthesis. We then used these synthetic HA and NA genes to transfect Madin-Darby canine kidney (MDCK) cells that were qualified for vaccine manufacture with viral RNA expression constructs encoding HA and NA and plasmid DNAs encoding viral backbone genes. Viruses for use in vaccines were rescued from these MDCK cells. We performed this rescue with improved vaccine virus backbones, increasing the yield of the essential vaccine antigen, HA. Generation of synthetic vaccine seeds, together with more efficient vaccine release assays, would accelerate responses to influenza pandemics through a system of instantaneous electronic data exchange followed by real-time, geographically dispersed vaccine production.