叙利亚地鼠作为狂犬病暴露后免疫动物模型的研究

Study on Syrian hamster as an animal model for post-exposure prophylaxis of rabies

目的对叙利亚地鼠（地鼠）作为狂犬病暴露后疫苗免疫效果动物模型的可行性进行研究。方法将狂犬病病毒CVS株和CTN-1V株分别肌内感染不同周龄的地鼠和小鼠，观察动物对不同毒株的敏感性。用直接免疫荧光法检测CVS株进入地鼠脑组织的情况；用快速荧光灶抑制试验检测血清中和抗体。以不同病毒量CVS株感染8周龄雌性地鼠，确定暴露时病毒的最佳感染剂量。对暴露后地鼠用疫苗进行免疫，观察疫苗的保护效果。结果地鼠感染后7d左右出现狂犬病临床症状，同一病毒株对地鼠的致病力比小鼠强[6．4～8．0 lg半数致死量（LD50）／ml对3．4～6．5 lgLD50／ml]；3周龄和8周龄地鼠对病毒的敏感性无差异。感染后5～6d病毒进入地鼠脑组织。以3．8～4．0 lg小鼠脑内半数致死量（MICLD50）／ml的CVS株感染后6～7d，地鼠血清中检出中和抗体。暴露后疫苗免疫结果显示，不同疫苗具有不同程度的保护效果。结论地鼠对狂犬病病毒神经外途径感染敏感，临床症状典型，潜伏期恒定，感染后免疫血清抗体应答出现早，具备作为暴露后疫苗免疫动物模型的条件。

Objective To study feasibility of Syrian hamster （hamster） used as an animal model for evaluation of rabies vaccine efficacy in post-exposure prophylaxis. Methods The sensitivity to different virus strains was investigated in different ages of hamsters and mice infected intramuscularly with CVS and CTN-1V strains, respectively. Direct immunofluorescence assay and rapid fluorescent focus inhibition test were used to detect virus titers in brain and antibody titers in serum, respectively. Hamsters aged 8 weeks were infected with different titers of CVS strain to determine the optimal infection dose. Protective efficacy of rabies vaccines was observed in hamster by post-exposure immunization. Results Rabies symptoms occurred around 7 d after infection in hamsters. Pathogenicity of rabies virus was higher in hamsters than that in mice^6. 4-8. 0 lg median lethal dose （LD50）/ml vs. 3. 4-6. 5 lgLD50/ml]. No difference of sensitivity to the virus was found between hamsters aged 3 weeks and 8 weeks. The virus entered brain tissue 5-6 d post-infection. Serum neutralizing antibody was detectable 6-7 d after infection with 3. 8-4. 0 lg mouse intracerebral LD50/ml of CVS strain. Various protective effieacies were observed in hamsters immunized with different vaccines. Conclusions Hamster is very sensitive to rabies virus by peripheral infection with typical clinical symptoms and constant incubation period. The antibody response appears early. Therefore, hamster is qualified as an animal model for post-exposure prophylaxis of rabies.