[重组结核疫苗AEC/BC02接种结核分枝杆菌感染豚鼠的郭霍现象分析]

[Analysis of Koch phenomenon of Mycobacterium tuberculosis-infected guinea pigs vaccinated with recombinant tuberculosis vaccine AEC/BC02].

作者信息

Lu J B, Cheng B W, Deng H Q, Su C, Shen X B, Du W X, Yang L, Wang G Z, Xu M

机构信息

Division of Tuberculosis Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2016 Jul;39(7):524-8. doi: 10.3760/cma.j.issn.1001-0939.2016.07.007.

DOI:10.3760/cma.j.issn.1001-0939.2016.07.007

PMID:27430923

Abstract

OBJECTIVE

To observe the Koch phenomenon of Mycobacterium tuberculosis(MTB)-infected guinea pigs after vaccinated with killed H37Ra bacteria or tuberculosis vaccine candidate AEC/BC02.

METHODS

Eighteen guinea pigs were challenged subcutaneously with 5.0×10(3) CFU MTB and after 40 days were divided into 3 groups (6 per group): NS group, AEC/BC02 group and H37Ra group, which were injected intramuscularly 3 times at 1 day interval with normal saline, AEC/BC02 vaccine and killed H37Ra bacteria respectively. Three weeks after the first vaccination, all guinea pigs were sacrificed to evaluate gross pathological scores for liver, spleen and lung, bacterial loads in lung and spleen, and lung inflammation.

RESULTS

The gross pathological score in H37Ra group (48±26) was lower than that in NS group(62±15), but the difference was not significant (t=1.093, P=0.300). The AEC/BC02 group had a significantly lower gross pathological score (36±15) than NS group (t=2.980, P=0.014). No significant difference between H37Ra group and AEC/BC02 group was observed (t=1.009, P=0.337). The spleen bacterial load [(5.31±0.80) log10 CFU]in H37Ra group was slightly lower than that in NS group[(5.57±0.75) log10 CFU] but the difference was not significant (t=1.581, P=0.574). In AEC/BC02 group bacterial load in the spleen was (4.64±0.64) log10 CFU and significantly lower than NS group (t=2.306, P=0.044) and no significant difference between H37Ra group and AEC/BC02 group was observed (t=1.602, P=0.140). Meanwhile, the lung bacterial load in AEC/BC02 group was (3.71±1.01) log10 CFU and in H37Ra group was (3.82±1.25) log10 CFU. Compared to (4.15±0.69) log10 CFU in the NS group, no significant differences were found (t=0.881, P=0.399; t=0.566, P=0.584, respectively). For the lung inflammation, the inflamed areas in H37Ra group were significantly larger [(33.0±4.4%)] than those in both NS group [(14.8±8.4) %, t=4.719, P=0.001] and AEC/BC02 group [(14.8±8.4) %, t=3.616, P=0.005], and no significant differences were seen between AEC/BC02 group and NS group (t=1.041, P=0.322).

CONCLUSION

The lung inflammation indicated that killed H37Ra bacteria evoked an obvious Koch reaction in the MTB-infected guinea pigs, whereas AEC/BC02 vaccine showed a low risk of causing Koch phenomenon.

摘要

目的

观察用灭活的H37Ra菌或结核疫苗候选物AEC/BC02免疫后结核分枝杆菌（MTB）感染豚鼠的郭霍现象。

方法

18只豚鼠皮下接种5.0×10(3) CFU MTB，40天后分为3组（每组6只）：生理盐水组、AEC/BC02组和H37Ra组，分别于1天间隔肌肉注射3次生理盐水、AEC/BC02疫苗和灭活的H37Ra菌。首次接种3周后，处死所有豚鼠，评估肝脏、脾脏和肺的大体病理评分、肺和脾脏中的细菌载量以及肺部炎症。

结果

H37Ra组的大体病理评分（48±26）低于生理盐水组（62±15），但差异无统计学意义（t=1.093，P=0.300）。AEC/BC02组的大体病理评分（36±15）显著低于生理盐水组（t=2.980，P=0.014）。H37Ra组与AEC/BC02组之间未观察到显著差异（t=1.009，P=0.337）。H37Ra组脾脏细菌载量[（5.31±0.80）log10 CFU]略低于生理盐水组[（5.57±0.75）log10 CFU]，但差异无统计学意义（t=1.581，P=0.574）。AEC/BC02组脾脏细菌载量为（4.64±0.64）log10 CFU，显著低于生理盐水组（t=2.306，P=0.044），H37Ra组与AEC/BC02组之间未观察到显著差异（t=1.602，P=0.140）。同时，AEC/BC02组肺部细菌载量为（3.71±1.01）log10 CFU，H37Ra组为（3.82±1.25）log10 CFU。与生理盐水组的（4.15±0.69）log10 CFU相比，差异均无统计学意义（分别为t=0.881，P=0.399；t=0.566，P=0.584）。对于肺部炎症，H37Ra组的炎症面积[（33.0±4.4）%]显著大于生理盐水组[（14.8±8.4）%，t=4.719，P=0.O01]和AEC/BC02组[（14.8±8.4）%，t=3.616，P=0.005]，AEC/BC02组与生理盐水组之间未观察到显著差异（t=1.041，P=0.322）。