金黄地鼠作为狂犬病暴露后疫苗免疫动物模型的应用

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目的以金黄地鼠作为动物模型,评价不同种类狂犬病疫苗在暴露后免疫中的保护效果。方法将不同类型狂犬病疫苗分别免疫两组金黄地鼠,一组为未感染过病毒的健康动物(Pr EP),另一组为感染过CVS株的动物(PEP),免疫后不同时间点通过心脏穿刺采血,RFFIT法测定血清抗体效价。对PEP组动物同时观察其死亡情况,分析各动物抗体水平与保护效果的相关性。另以4.0 lg MICLD_(50)/ml的CVS狂犬病固定毒株感染金黄地鼠左腿腓肠肌,每只0.2 ml,6 h后开始以不同类型狂犬病疫苗按0、3、7、14 d程序免疫,观察疫苗对动物的保护效果。结果暴露后免疫组(PEP)的血清抗体可在第4天出现阳性,第5天达100%,以后持续维持较高水平。未感染的暴露前免疫(Pr EP)动物的抗体水平从第4天开始一直较PEP组低。但PEP组中不同疫苗免疫的各动物中均观察到免疫后第4天及以后的抗体水平与最终该动物的发病死亡无相关性。高效价人用狂犬病疫苗的免疫保护率为80%,但疫苗原液分别稀释2倍和5倍后,保护率分别降至30%和20%。疫苗加PIKA佐剂作相同倍数稀释后,保护率可达80%,疫苗联合使用免疫球蛋白,暴露后保护率可达100%,未免疫的感染对照组动物的死亡率在90%左右。结论以金黄地鼠作为狂犬病暴露后免疫的动物模型可对不同质量疫苗作出有效评价。疫苗的效价与暴露后免疫中的保护作用有相关性,疫苗联合使用免疫球蛋白注射是最佳的暴露后免疫方案;PIKA佐剂在降低疫苗抗原量的同时提高了疫苗的保护作用;暴露后抗体水平未显示与保护效果具有相关性。 Objective To evaluate the protective effects of different types of rabies vaccines on post-exposure immunization using golden hamster as an animal model. Methods Two groups of golden hamsters were immunized with different types of rabies vaccine respectively. One group was healthy animal (Pr EP) without virus infection and the other group was infected with CVS strain (PEP). After vaccination, Blood was collected by puncture and serum antibody titer was determined by RFFIT. PEP group of animals were observed at the same time the death of the situation, analysis of animal antibody levels and the protective effect of the correlation. In addition, the left hamster gastrocnemius of golden hamster was infected with 4.0 lg MICLD_ (50) / ml CVS rabies fixed strain, 0.2 ml each. After 6 h, different types of rabies vaccine were vaccinated by 0, 3, Observe the protective effect of the vaccine on animals. Results Serum antibodies of the immunized group (PEP) showed positive on the 4th day and reached 100% on the 5th day, and remained high afterwards. Antibody levels in uninfected pre-exposure (PrEP) animals remained consistently lower from day 4 than in the PEP group. However, there was no correlation between the level of antibody on day 4 and after immunization and the eventual death of the animals in each group immunized with different vaccines in the PEP group. The high rate of human rabies vaccine immunization protection rate of 80%, but the vaccine stock solution were diluted 2 times and 5 times, the protection rate dropped to 30% and 20%. Vaccination with PIKA adjuvant for the same multiple dilution, the protection rate of up to 80%, the combination of immunoglobulin vaccine, after exposure protection up to 100%, uninfected control animals infected with the mortality rate of about 90%. Conclusions The golden hamster can effectively evaluate different quality vaccines after being exposed to rabies as an immunized animal model. The potency of the vaccine was correlated with the protective effect of post-exposure immunization. Immunization with immunoglobulin injection was the best post-exposure immunization protocol; PIKA adjuvant increased the vaccine's protective effect while reducing the vaccine antigen amount; exposure Post-antibody levels have not been shown to correlate with protective effects.
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