VARYING REACTIVITIES OF MONOCLONAL ANTIBODIES WITH THE SAME POLIO VACCINE

相同脊髓灰质炎疫苗的单克隆抗体的不同反应性

• 批准号: 3811260
• 负责人: L A SAWYER
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3811260
• 关键词: biological products; diagnosis quality /standard; diagnostic tests; drug screening /evaluation; enzyme linked immunosorbent assay; immunological substance; monoclonal antibody; poliomyelitis vaccine

Polio vaccines are tested in our laboratory for potency. Trivalent vaccines are tested for all three polio types (1, 2, and 3). An ELISA procedure developed in our laboratory has recently been updated and standardized. Monoclonal antibodies directed against the D antigen are used as the detecting antibodies in the sandwich. We found two vaccine lots formulated from the same type 2 concentrate to have very different levels of type 2 D antigen in the final container when tested using our standard type 2 monoclonal antibody. This difference was also observed at the final bulk stage, but not at the trivalent concentrate stage. Interestingly, a different type 2 D antigen specific monoclonal antibody indicated not only adequate levels of D antigen in the lot which had barely detectable levels using the first, standard monoclonal antibody, but higher levels than the other lot made from the same type 2 concentrate. In the process of trying to elucidate the cause of this distinct difference in reactivity we reviewed the manufacturing records and the two vaccine lots appear to have been made using identical procedures and components. We tested samples set aside for stability testing covering a period of up to 56 months and samples from a mock production of the vaccine lot in question. The data on stability are difficult to interpret. Although vaccines stored the longest have lower potency than more recently produced vaccines, we do not know the starting potency of these vaccines using the current test as it was not available at the time of their production. The apparent change in potency as measured by the standard monoclonal antibody was not reproduced in the mock production samples. Whether this change in one D epitope is important in terms of vaccine potency and efficacy is not clear. These results indicate that there may be some inconsistency in manufacture which caused the difference between lots. Further examination of other possible causes will be pursued.

脊髓灰质炎疫苗在我们的实验室进行效力测试。三价疫苗 对所有三种脊髓灰质炎类型(1、2和3)进行测试。一种酶联免疫吸附试验 在我们实验室开发的，最近进行了更新和标准化。 针对D抗原的单抗被用作 检测三明治中的抗体。我们发现了两批配方疫苗 从相同的类型2浓缩到有非常不同的类型2D水平 使用我们的标准型2进行测试时，最终容器中的抗原 单抗。这一差异也在最后一批中观察到 阶段，但不是在三价浓缩阶段。 有趣的是，另一种不同类型的2D抗原特异性单抗 不仅表明在这批几乎没有 使用第一种标准单抗可检测到的水平，但更高 比由相同类型2精矿制成的其他批次的水平更高。在 试图阐明这种明显差异的原因的过程 反应性我们检查了生产记录和两批疫苗 似乎是使用相同的程序和部件制造的。我们 留作稳定性测试的测试样本，有效期最长可达 56个月和一批模拟生产的疫苗的样本 问题。有关稳定性的数据很难解释。 尽管储存时间最长的疫苗效力低于最近 生产的疫苗，我们不知道这些疫苗的起始效力 使用当前测试，因为它在他们的 制作。按标准衡量的效力的明显变化 在模拟生产的样品中不能复制单抗。 就疫苗而言，一个D表位的这种变化是否重要 效力和疗效尚不清楚。这些结果表明，可能存在 制造过程中的一些不一致，导致了批次之间的差异。 我们会进一步调查其他可能的原因。