摘要
目的建立适合评价BCG初免加强型结核新疫苗的豚鼠动物模型，并用新型结核疫苗进行验证性评价。方法按初免-加免间隔时间，分为短期（间隔14周）评价和长期（间隔54周）评价两次实验。短期评价中BCG免疫14周后豚鼠给予重组结核疫苗（ AEC/BC02）加强免疫2次；长期评价中BCG免疫54周后豚鼠给予重组结核疫苗（ AEC/BC02）加强免疫3次。两次实验中均设置阴性对照组（NS→NS）和卡介苗对照组（BCG→NS）。末次加强免疫1周后，所有豚鼠攻毒结核分枝杆菌（ M．tuberculosis，Mtb），感染6～7周后，处死豚鼠，评价豚鼠肝、脾、肺综合病变指数，并检测脾脏活菌负荷量。结果短期评价：疫苗加强组豚鼠肝、脾、肺综合病变指数评分（3．33±5．00）低于卡介苗对照组（5．56±7．27）和阴性对照组（47．00±28．11），疫苗加强组和卡介苗对照组与阴性对照组相比均有统计学差异（分别P＝0．0001和P＝0．0002），但疫苗加强组与卡介苗对照组无统计学差异（ P＝0．4294）。疫苗加强组豚鼠的脾菌分离数对数（log10CFU）平均值为0．78±1．55，低于卡介苗对照组1．06±1．87，但差异无统计学意义；低于阴性对照组5．47±0．61，差异有统计学意义（P＝0．0003）。长期评价：疫苗加强组豚鼠肝、脾、肺综合病变指数评分（5．0±7．6）低于卡介苗对照组（14．4±13．5）和阴性对照组（56．9±14．1），差异有统计学意义（分别P＝0．0394和P＜0．0001）；疫苗加强组豚鼠的脾菌分离数对数平均值为1．00±1．86，低于卡介苗对照组的1．46±1．94，但差异无统计学意义；低于阴性对照组的5．43±0．56，差异有统计学意义（P＝0．01）。卡介苗对照组豚鼠的脾菌分离数对数平均值为1．46±1．94，低于阴性对照组的5．43±0．56，差异有统计学意义（P＝0．0089）。结论综合对比短期评价与长期评价两次实验，评价初免加强型新疫苗的动物模型应适当延长初免和加强免疫的间隔时间。
Objective To establish a suitable guinea pig model for evaluating the protective effects of new TB vaccines in BCG prime-boost regimen .Methods Two different immunization strategies by using the recombinant TB vaccine were employed to boost BCG primed guinea pigs in this study .One was for short-term evaluation with 14 weeks interval between prime and boost immunization and another was for long -term evaluation with 54 weeks interval .In the short-term evaluation group , guinea pigs were boosted twice with the recombinant TB vaccine （ AEC/BC02 ） in every two weeks , while guinea pigs in the long-term evaluation group were boosted for three times with two weeks interval between each injection .A negative con-trol group （ NS→NS） and a BCG control group （ BCG→NS） were both set up in two evaluation groups .One week after the last immunization , all guinea pigs were challenged with M.tuberculosis.Six to seven weeks after bacteria challenge , all animals were euthanized and dissected to evaluate lesion scores of liver , spleen and lung, as well as the viable bacterial load in spleen .Results In the short-term evaluation group , the le-sion scores in those boosted with vaccine （3.33±5.00） was lower than that of BCG control group （5.56± 7.27） （P〉0.05） and negative control group （47.00±28.11） （P=0.0001）.The difference between BCG control group and negative control group in lesion score was also significant .The animals in vaccine boosted group had lower bacterial loads （0.78±1.55 log10 ） in spleen than that in BCG control group （1.06±1.87） （P〉0.05） and negative control group （5.47±0.61） （P=0.0003）.In the long-term evaluation group, the lesion score in those boosted with vaccine was lower （5.0±7.6） than that in BCG control group （14.4± 13.5） （P=0.0394） and negative control group （56.9±14.1） （P〈0.0001）.The animals in vaccine boos-ted group （1.00±1.86 log10） had lower bacterial loads in spleen than that in BCG control group （1.46± 1.94） （P〉0.05） and negative control group （5.43±0.56） （P=0.01）.There was a significant difference in bacterial load between BCG control group and negative group （P=0.0089）.Conclusion The results suggest that the interval time between BCG-prime and boost immunization should be properly prolonged in the guinea pig model used for evaluating the protective effects of new TB vaccines in BCG prime -boost regimen .
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
2013年第12期893-899,共7页
Chinese Journal of Microbiology and Immunology
关键词
结核
初免加强
动物模型
豚鼠
重组结核疫苗
Tuberculosis
BCG-prime boost regimen
Animal model
Guinea pig
Recombinant TB vaccine
