Enhanced Growth of Influenza Vaccine Seed Viruses in Vero Cells Mediated by Broadening the Optimal pH Range for Virus Membrane Fusion
Enhanced Growth of Influenza Vaccine Seed Viruses in Vero Cells Mediated by Broadening the Optimal pH Range for Virus Membrane Fusion
复制标题
DOI：
10.1128/jvi.06009-11
复制
发表时间：
2012-02-01
影响因子：
5.4
通讯作者：
Kawaoka, Yoshihiro
中科院分区：
文献类型：
--
作者：
Murakami, Shin;Horimoto, Taisuke;Kawaoka, Yoshihiro
接种疫苗是对抗流感最有效的预防措施之一。基于细胞培养的流感疫苗在正常情况和紧急情况下（如2009年大流行期间）的稳定疫苗生产中发挥着重要作用。世界卫生组织推荐非洲绿色猴Vero细胞作为生产人用流感疫苗的安全基质。然而，流感疫苗种子病毒在Vero细胞中的生长偶尔是次优的，这限制了它们用于增强疫苗生产的有用性。在这里，我们提出了一个战略，通过改变血凝素（HA）分子的HA2亚基的干细胞区域的氨基酸残基，在Vero细胞中增强生长的疫苗种子病毒的发展。该突变优化了Vero细胞中HA介导的膜融合的pH，并使细胞系中的病毒生长增强了100至1，000倍，为基于细胞培养的流感疫苗提供了有希望的策略。
Vaccination is one of the most effective preventive measures to combat influenza. Prospectively, cell culture-based influenza vaccines play an important role for robust vaccine production in both normal settings and urgent situations, such as during the 2009 pandemic. African green monkey Vero cells are recommended by the World Health Organization as a safe substrate for influenza vaccine production for human use. However, the growth of influenza vaccine seed viruses is occasionally suboptimal in Vero cells, which places limitations on their usefulness for enhanced vaccine production. Here, we present a strategy for the development of vaccine seed viruses with enhanced growth in Vero cells by changing an amino acid residue in the stem region of the HA2 subunit of the hemagglutinin (HA) molecule. This mutation optimized the pH for HA-mediated membrane fusion in Vero cells and enhanced virus growth 100 to 1,000 times in the cell line, providing a promising strategy for cell culture-based influenza vaccines.