Bellalou J, Relyveld E H
Ann Microbiol (Paris). 1984 Jul-Aug;135B(1):101-10. doi: 10.1016/s0769-2609(84)80047-2.
Conditions for growing Bordetella pertussis bacteria in fermentors were studied for the purpose of producing highly protective vaccines. Bacteria with high protective potency were obtained in fermentors when the inoculum consisted of a dense suspension of young B. pertussis cells grown on Bordet-Gengou agar plates. When the time of cultivation in fermentors exceeded 30 h, bacteria harvested showed lower protective potency activity and lower levels of histamine sensitizing factor (HSF) and leukocytosis promoting factor (LPF), indicating that the optimal time for collection is at the end of the logarithmic growth phase. In fermentors, the ATP concentration in the bacterial cells increased from the time of inoculation until the end of the logarithmic growth phase. At the late logarithmic growth phase, the amounts of ATP, HSF, LPF and protective antigen declined rapidly. ATP kinetics thus provides a way of predicting the immunogenicity of vaccines. These results may be applicable to the production of vaccines exhibiting high protective activity at low bacterial concentrations, and to the preparation of soluble vaccines resulting from high-yield extraction of protective antigens. A correlation between the potency and LPF activity of vaccines was established for use in the rapid screening of vaccines for protective activity.
为生产具有高度保护性的疫苗，对在发酵罐中培养百日咳博德特氏菌的条件进行了研究。当接种物为由在博-金氏琼脂平板上生长的年轻百日咳博德特氏菌细胞组成的浓悬液时，可在发酵罐中获得具有高保护效力的细菌。当在发酵罐中的培养时间超过30小时时，收获的细菌显示出较低的保护效力活性以及较低水平的组胺致敏因子（HSF）和白细胞增多促进因子（LPF），这表明最佳收集时间是在对数生长期结束时。在发酵罐中，细菌细胞中的ATP浓度从接种时起直至对数生长期结束时都会增加。在对数生长后期，ATP、HSF、LPF和保护性抗原的量迅速下降。因此，ATP动力学提供了一种预测疫苗免疫原性的方法。这些结果可能适用于在低细菌浓度下表现出高保护活性的疫苗的生产，以及适用于通过高产提取保护性抗原而获得的可溶性疫苗的制备。建立了疫苗效力与LPF活性之间的相关性，用于快速筛选具有保护活性的疫苗。
