Identification of Influenza A/PR/8/34 Donor Viruses Imparting High Hemagglutinin Yields to Candidate Vaccine Viruses in Eggs.
Identification of Influenza A/PR/8/34 Donor Viruses Imparting High Hemagglutinin Yields to Candidate Vaccine Viruses in Eggs.
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DOI：
10.1371/journal.pone.0128982
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Donis RO
中科院分区：
文献类型：
--
作者：
Johnson A;Chen LM;Winne E;Santana W;Metcalfe MG;Mateu-Petit G;Ridenour C;Hossain MJ;Villanueva J;Zaki SR;Williams TL;Cox NJ;Barr JR;Donis RO
从2009年H1N1大流行中吸取的重要教训之一是，高产流感疫苗病毒对于在鸡蛋中有效和及时地生产大流行疫苗至关重要。目前的季节性和大流行前疫苗病毒通过经典重配或反向遗传学产生。这两种方法都利用高生长病毒，通常是A/波多黎各/8/1934（PR 8），作为所有或大部分内部基因的供体，以及推荐包含在疫苗中的野生型病毒，以贡献编码表面糖蛋白的血凝素（HA）和神经氨酸酶（NA）基因。由于通过连续的卵传代进行广泛适应，在过去的几十年中，不同的实验室已经选择了具有不同基因序列和高生长特性的PR 8病毒。这些相关但不同的内部PR 8基因对疫苗病毒在鸡蛋中生长的影响以前尚未研究过。在这里，我们使用反向遗传学系统地分析了具有3种不同PR 8骨架的重配病毒的生长和HA抗原产量。产生了一组9种不同的HA/NA基因对与3种不同的PR 8内部基因谱系（27种重组病毒）中的每一种的组合以评估它们的性能。病毒和HA产量测定表明，PR 8内部基因影响大多数亚型的HA产量。尽管在所有候选疫苗病毒中没有单个PR 8内部基因组优于其他基因组，但特异性PR 8骨架与单个HA/NA对的组合证明了HA产率的提高，从而提高了疫苗生产的速度。这些发现可能对季节性疫苗的生产和大流行期间的快速全球疫苗反应都很重要。
One of the important lessons learned from the 2009 H1N1 pandemic is that a high yield influenza vaccine virus is essential for efficient and timely production of pandemic vaccines in eggs. The current seasonal and pre-pandemic vaccine viruses are generated either by classical reassortment or reverse genetics. Both approaches utilize a high growth virus, generally A/Puerto Rico/8/1934 (PR8), as the donor of all or most of the internal genes, and the wild type virus recommended for inclusion in the vaccine to contribute the hemagglutinin (HA) and neuraminidase (NA) genes encoding the surface glycoproteins. As a result of extensive adaptation through sequential egg passaging, PR8 viruses with different gene sequences and high growth properties have been selected at different laboratories in past decades. The effect of these related but distinct internal PR8 genes on the growth of vaccine viruses in eggs has not been examined previously. Here, we use reverse genetics to analyze systematically the growth and HA antigen yield of reassortant viruses with 3 different PR8 backbones. A panel of 9 different HA/NA gene pairs in combination with each of the 3 different lineages of PR8 internal genes (27 reassortant viruses) was generated to evaluate their performance. Virus and HA yield assays showed that the PR8 internal genes influence HA yields in most subtypes. Although no single PR8 internal gene set outperformed the others in all candidate vaccine viruses, a combination of specific PR8 backbone with individual HA/NA pairs demonstrated improved HA yield and consequently the speed of vaccine production. These findings may be important both for production of seasonal vaccines and for a rapid global vaccine response during a pandemic.
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流感病毒疫苗：2009年H1N1大流行的教训。
影响因子：
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作者：
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通讯作者：
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发表时间：
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影响因子：
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作者：
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影响因子：
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