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目的重组亚牛痘病毒载体疫苗作为卡介苗的加强疫苗对结核病的免疫预防效果。方法将18只雌性中国恒河猴随机分为3组:BCG、BCG+A和BCG+AE组,每组6只,BCG+A和BCG+AE组用4×10~5 CFU的BCG经皮内初免后9周,分别用重组亚牛痘病毒MVA-Ag85a(A)或MVA-Ag85a-ESAT6(AE),按1×10~9 PFU/只的剂量通过皮内加强免疫,BCG组仅用BCG免疫,另设未免疫组(Non-V组):3只雄性中国恒河猴。加强免疫后9周,用结核分枝杆菌H37Rv株通过纤维支气管镜感染所有实验猴右肺下叶,攻毒剂量为41 CFU/只。经24周定期观察记录实验动物的临床表现,并采血进行血清学和免疫学检测。实验猴死亡或第24周处死后,全部尸检并进行病理学组织评分、组织细菌载量计数等检测。结果在实验终点,Non-V组仅存活1只实验猴,而免疫组3组的存活率均为100%。体外免疫试验中,经重组痘苗病毒免疫的试验组表现出抗原特异性IFNγ明显升高(P<0.05);组织病理总评分和细菌载量测定显示,BCG+A组优于BCG组,而BCG+AE与BCG组比较,未表现出优势。结论重组痘苗病毒MVA-Ag85a和MVA-Ag85a-ESAT6均能诱导抗原特异性IFNγ分泌,BCG+A组较BCG单次免疫组有更好的免疫保护趋势;BCG+AE组未表现出较BCG组更好的免疫保护效果。
Objective To investigate the immunoprophylactic effect of recombinant vaccinia virus vaccines as a booster vaccine against tuberculosis. Methods Eighteen female Chinese rhesus monkeys were randomly divided into 3 groups: BCG, BCG + A and BCG + AE groups, 6 in each. BCG + A and BCG + AE groups were treated with 4 × 10 ~ 5 CFU of BCG percutaneous Within 9 weeks after initial immunization, mice were immunized intradermally with 1 × 10 ~ 9 PFU / MVA-Ag85a (A) or MVA-Ag85a-ESAT6 (AE) BCG immunization, another non-immune group (Non-V group): 3 male Chinese rhesus monkeys. Nine weeks after booster immunization, all experimental monkey lower lungs were infected by Mycobacterium tuberculosis H37Rv strain via bronchoscopy at a dose of 41 CFU / animal. The clinical manifestations of experimental animals were recorded after 24 weeks of regular observation, and blood was collected for serological and immunological tests. After the death of experimental monkeys or sacrificed at the 24th week, all autopsy and pathological tissue score, tissue bacterial count and other tests. Results At the end of the experiment, only one experimental monkey survived in the Non-V group, while the survival rates in the three immunized groups were 100%. In the in vitro immunoassay, the group immunized with recombinant vaccinia virus showed significantly higher antigen-specific IFNγ (P <0.05). The histopathological score and bacterial load showed that the BCG + A group was superior to the BCG group and the BCG group + AE did not show any advantage over the BCG group. CONCLUSION: Recombinant vaccinia virus MVA-Ag85a and MVA-Ag85a-ESAT6 can both induce antigen-specific IFNγ secretion. BCG + A group has a better immune protection tendency than BCG single immunization group. BCG + AE group did not show any significant difference compared with BCG group Better immune protection effect.