BACKGROUND Foot-and-mouth disease is a highly contagious and economically devastating disease with endemic occurrence in many parts of the world. Vaccination is the method of choice to eradicate the disease and to limit the viral spread. The vaccine production process is based on mammalian cell culture, in which the viral yield varies in dependence of the composition of the culture media. For foot-and-mouth disease virus (FMDV), very little is known about the culture media components that are necessary to grow the virus to high titers in cell culture. RESULTS This study examined the influence of increasing concentrations of glucose, glutamine, ammonium chloride and different cell densities on the yield of FMDV. While an excess of glucose or glutamine does not affect the viral yield, increasing cell density reduces the viral titer by a log10 step at a cell density of 3 × 106 cells/mL. This can be mitigated by performing a 100% media exchange before infection of the cells. CONCLUSIONS The reasons for the diminished viral growth, if no complete media exchange has been performed prior to infection, remain unclear and further studies are necessary to investigate the causes more deeply. For now, the results argue for a vaccine production process with 100% media exchange to reliably obtain high viral titers.

中文翻译：

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研究用于最佳口蹄疫病毒生产的细胞培养条件。

背景技术口蹄疫是一种高度传染性和经济破坏性的疾病，在世界许多地方流行。接种疫苗是根除疾病和限制病毒传播的首选方法。疫苗的生产过程基于哺乳动物细胞培养，其中病毒产量取决于培养基的组成而变化。对于口蹄疫病毒（FMDV），对于使病毒在细胞培养中生长至高滴度所必需的培养基成分知之甚少。结果这项研究检查了葡萄糖，谷氨酰胺，氯化铵浓度增加和不同细胞密度对FMDV产量的影响。虽然过量的葡萄糖或谷氨酰胺不会影响病毒产量，在3×106细胞/ mL的细胞密度下，增加的细胞密度可通过log10步降低病毒滴度。这可以通过在感染细胞之前进行100％的培养基交换来缓解。结论如果在感染前没有进行完整的培养基交换，病毒生长减少的原因尚不清楚，因此有必要进一步研究以更深入地调查病因。目前，结果表明疫苗生产过程必须通过100％的培养基交换才能可靠地获得高病毒滴度。尚不清楚，需要进一步研究以更深入地调查原因。目前，结果表明疫苗生产过程必须通过100％的培养基交换才能可靠地获得高病毒滴度。尚不清楚，需要进一步研究以更深入地调查原因。目前，结果表明疫苗生产过程必须通过100％的培养基交换才能可靠地获得高病毒滴度。