人用皮内注射布氏菌活疫苗毒理及药效学研究

Toxicology and Efficacy of Live Brucella Vaccine for Intradermal Injection

目的 研究人用皮内注射布氏菌活疫苗的毒理及药效学作用,以评价其可行性.方法 对布氏菌活疫苗进行小白鼠急性毒性试验、局部刺激试验、全身过敏试验、长期毒性试验及豚鼠皮肤变态反应试验并免疫小鼠,进行血清抗体检测.结果 小鼠皮内注射布氏菌活疫苗的最大耐受量为1.0×10^9个菌,用布氏菌素注射足底,可引起明显的迟发型变态反应.局部刺激试验,只有注射1.0×10^9个菌的部位会在48 h后化脓,但在1～2周内可自愈.全身过敏试验均未出现任何异常反应,毒性试验、各项血常规、血生化检查均未见显著差异,各脏器组织的病理学检查亦未见病理改变.免疫12周后,对豚鼠骨髓造血细胞亦无影响.对皮内免疫12周的豚鼠作背部皮肤变态反应试验,24～48 h结果为阳性.皮内免疫小鼠14 d后可测得小鼠体内有抗体产生,50 d后测得小鼠体内抗体均呈强阳性,对照组小鼠14 d与50 d抗体检测均为阴性.结论 毒理和药效学试验结果显示,布氏菌活疫苗用皮内注射的途径进行免疫是可行的.

Objective To study the toxicology and efficacy and evaluate the feasibility of live Brucella vaccine for intradermal injection. Methods Perform acute toxicity test in mice, as well as local stimulation test, systemic anaphylaxis test,long-term toxicity test and skin allergic reaction test in guinea pigs on live Brucella vaccine. Immunize mice with the vaccine and determine the serum antibody. Results The maximal tolerated dose of live Brucella vaccine for intradermal injection in mice was 1.0 ×10^9 bacteria. Delayed type hypersensitivity （DTH） was caused by injection with live Brucella vaccine into the sole of feet of mice. In local stimulation test, pyogenesis appeared only at the site 48 h after injection with 1.0 ×10^9 bacteria but disappeared within 1-2 weeks. No adverse reaction was observed in systemic anaphylaxis test. In toxicity test, all the routine serological and serobiochemical indexes of guinea pigs in test group showed no significant different from those in control group. No pathological change was observed in the organs of guinea pigs. The immunization with live Brucella vaccine showed no significant influence on the bone marrow hematopoieti cells of guinea pigs. The skin allergic reaction test on guinea pigs 12 weeks after injection showed a positive result. The determination results of serum antibody were positive in the mice 14 d after and strong positive 50 d after i.d. injection with the vaccine. However,both the determination results were negative in control mice. Conclusion Both toxicology and efficacy tests proved that it was feasible to inoculate live Brucella vaccine by intradermal injection.