狂犬病-干扰素联合制剂的免疫原性及治疗作用

Immunogenicity and Curative Effect of Rabies Vaccine-Interferon Combined Preparation

目的 研究狂犬病疫苗和干扰素组成的联合制剂的免疫原性和暴露后的治疗作用。方法 将人用精制Vero细胞狂犬病疫苗（PVCRV）和基因工程干扰素（rHuIFNs）按一定比例配制成联合制剂,进行安全和效力试验,以PVCRV-HuIFNs和PVCRV分别免疫小鼠,在第1针免疫后9和18d,采用快速免疫荧光灶抑制试验,检测小鼠中和抗体水平,用MTT法检测特异的细胞毒作用（CTLs）。一定剂量的狂犬病病毒标准攻击株（CVS）肌肉感染小鼠后,分别用PVCRV-HuIFNs和PVCRV在0、3和7d皮内免疫感染小鼠,分别在末次免疫的第7和21d进行CTLs试验,并在30d内观察小鼠发病和死亡情况。结果 联合制剂安全有效,效价高于单一疫苗,在暴露前诱导的中和抗体水平与单一疫苗比较差异有显著意义;在暴露前后激发的CTL,联合制剂均高于单一疫苗,差异有显著意义。结论 联合制剂可用于狂犬病暴露后的免疫治疗。

Objective To study on the immunogenicity and curative effect of a combined preparation of recombinant interferon and rabies vaccine. Methods A combined preparation was prepared by mixing purified Vero cell rabies vaccine(PVCRV) and recombinant human interferon(rHuIFN)in a proper proportion and tested for safety and titer. The mice were immunized with PVCRV - rHuIFN and PVCRV respectively and bled 9 and 18d later for delecting neutralizing antibody and specific CTLs by rapid imrhunofulrescence focus inhibition test (RIFIL) and MTT method respectively. After being intramusculary challenged with CVS strain, the mice in experimental and control groups were intradermaly immunized with PVCRV - HuIFN and PVCRV for 3 times respectively on day 0,3 and 7 and tested for specific CTLs for 2 times on day 7 and 21 after the last immunization , and the morbidity and mortality of them within 30d were observed. Results The combined preparation was safe and effective, and the tiler of it was significantly higher than that of PVCRV. Compared with those induced by PVCRV alone, the pre - expose neutralizing antibody titers, as well as pre - and post - expose CTL levels induced by PVCRV - HuIFN were significantly high. Conclusion The combined preparation can be used for the post - expose immunotherapy of rabies.