STUDIES OF IPV IN MICE TO REPLACE TEST IN MONKEYS

小鼠 IPV 研究替代猴子试验

• 批准号: 3770313
• 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/3770313
• 关键词: active immunization; antibody formation; disease /disorder model; drug administration rate /duration; drug quality /standard; enzyme linked immunosorbent assay; hyperimmunization; laboratory mouse; method development; neutralizing antibody; nonhuman therapy evaluation; poliomyelitis; poliomyelitis vaccine; poliovirus; virus antigen

An international consensus as to the best method for measuring the potency of inactivated poliovirus vaccines (IPV) in vitro or in vivo has not yet been achieved. Laboratories do not agree on the most feasible animal model of potency and therefore laboratories use rats, guinea pigs, chickens or primates none of which are ideal for many reasons. In the U.S. and Canada, the monkey is required for the purpose of IPV lot release. Monkeys are given 3 injections at 7 day intervals. This hyper-immunization may obscure the antigenicity. The new purified vaccines induce an antibody response in monkeys that would rarely fail a vaccine lot even if the level of D Ag unit in the vaccine was lower than would be recommended for a human dose. For these reasons we are pursuing the identification of an appropriate animal model. We have selected the Balb/c mouse for further study. Based on the manufacturer's assigned potency, serial two-fold dilutions of trivalent IPV were prepared. The potency of the first vaccine dose was equivalent to a human dose. Six groups of mice were immunized intraperitoneally with one injection. Neutralizing antibodies were measured at 21 days. The potency of the six preparations of vaccine was measured by ELISA. The correlation between the amount of antigen injected and neutralizing antibody response was R=0.90, R=0.85, R=0.89 for poliotypes 1, 2 and 3 respectively. We are in the process of expanding this approach to confirm its usefulness.

国际上就测定效价的最佳方法达成了共识 灭活脊髓灰质炎病毒疫苗（IPV）的体外或体内研究尚未 办妥了一批多年想 实验室没有就最可行的动物模型达成一致 因此，实验室使用大鼠、豚鼠、鸡或 灵长类动物，因为很多原因，它们都不是理想的动物 在美国和加拿大， 需要猴用于IPV批放行。 猴子是 每隔7天注射3次。 这种过度免疫可能会掩盖 抗原性。 新的纯化疫苗诱导抗体反应， 即使D抗原单位水平降低， 低于人体推荐剂量。 为 基于这些原因，我们正在寻找合适的动物， 模型 我们选择Balb/c小鼠进行进一步研究。 基于 生产商指定效价，三价IPV的系列两倍稀释液 制备了 第一剂疫苗的效力相当于 人体剂量 六组小鼠腹腔内免疫一种 注射 在第21天测量中和抗体。 效价 用ELISA法测定了6种疫苗制剂的免疫原性。 的相关性 在注射的抗原量和中和抗体反应之间 1型、2型、3型的R分别为0.90、0.85、0.89。 我们 在扩大这一方法的过程中，以确认其有用性。