EFFECT OF PRESERVATIVES ON THE STABILITY OF INACTIVATED POLIOVIRUS VACCINE

我们已经建立了一种灵敏的ELISA法来测量细胞的效力 用鼠单抗制备脊髓灰质炎病毒三价疫苗 抗原检测。在IPV的常规测试中，我们发现了一批疫苗 用我们的标准试剂检测其类型2的成分非常低； 但与另一种2型单抗或 兔多克隆血清。我们正在与另一家实验室合作，因为 一个单独的研究项目，以确定我们的网站的特殊性 单克隆抗体。我们正在试图澄清 导致这种明显的表位特定变化的原因。我们回顾了 有关已知影响脊髓灰质炎病毒效力的化学物质的文献。我们 观察了硫柳汞对IPV效力的影响。准备工作 分别在37、25和4摄氏度三种温度下保存2周。这个 然后在第2、10和14天用酶联免疫吸附试验检测制剂的效力。 几天。在37摄氏度和4摄氏度下保存的疫苗制剂 在第14天接种到小鼠。我们发现IPV和IPV的组合 硫柳汞保存14天后会失去效力。 1型和2型脊髓灰质炎病毒的温度分别为25摄氏度和37摄氏度。 3型脊髓灰质炎病毒对硫柳汞不那么敏感，在以下情况下失去效力 疫苗只被保存在37摄氏度。这表明，处理 就IPV效力而言，使用硫柳汞的疫苗是非常重要的。 我们观察到我们的标准2型单抗似乎是 针对一个在存在中经历了变化的表位 硫柳汞。在体外测量的疫苗效力并没有 与小鼠的免疫原性相关。这些发现具有重要的意义 对联合疫苗制造商的影响，因为他们将需要 为了考虑每种防腐剂对鸡肉中抗原的影响 组合。

We have developed a sensitive ELISA assay for measuring the potency of trivalent poliovirus vaccines using mouse monoclonal antibodies for antigen detection. During routine tests of IPV we found a vaccine lot the type 2 component of which tested very low with our standard reagent; but gave satisfactory values with another type 2 monoclonal antibody or rabbit polyclonal sera. We are collaborating with another laboratory as a separate research project to identify the site specificity of our monoclonal antibodies. We are in the process of trying to elucidate the cause for this apparent epitope specific change. We reviewed the literature for chemicals known to affect the potency of poliovirus. We examined the effect of thimerosal on the potency of IPV. Preparations were held at three temperatures 37, 25 and 4 degrees C for 2 weeks. The preparations were then tested for potency by ELISA at 2, 10, and 14 days. Vaccine preparations held at 37 and 4 degrees degrees C were inoculated into mice on day 14. We found that combinations of IPV and thimerosal held for 14 days resulted in a loss of potency when kept at 25 degrees C as well as 37 degrees C for poliovirus types 1 and 2. Poliovirus type 3 was less sensitive to thimerosal and lost potency when the vaccine was held at 37 degrees C only. This suggested that handling of vaccines with thimerosal is very important in terms of IPV potency. We observed that our standard type 2 monoclonal antibody appeared to be directed against an epitope that had undergone changes in the presence of thimerosal. The potency of the vaccine measured in vitro did not correlate with immunogenicity in mice. These findings have important implications for manufacturers of combination vaccines as they will need to consider the effect of each preservative on the antigens in the combination.