Comparison of the toxicity and safety of protein derivatives from novel fusion strains of Mycobacterium tuberculosis
10.3969/j.issn.1002-2694.2025.00.055
- VernacularTitle:新型结核杆菌融合菌株蛋白衍生物毒性与安全性的比较研究
- Author:
Hao-qi XU
1
;
Jiang-tao DONG
;
Jie ZHANG
;
Fang WU
;
Su LIANG
;
Xiao-ling LIU
;
Lan-ru GAO
;
Ju WANG
;
Hui ZHANG
;
Jiang-dong WU
;
Le ZHANG
;
Xi-ling DENG
;
Wan-jiang ZHANG
Author Information
1. 石河子大学医学院病理生理学教研室/新疆地方与民族高发病教育部重点实验室,石河子 832002
- Publication Type:Journal Article
- Keywords:
tuberculosis;
B/R strain;
active protein;
toxicity;
safety
- From:
Chinese Journal of Zoonoses
2025;41(4):376-384
- CountryChina
- Language:Chinese
-
Abstract:
The objective of this study was to evaluate the toxicity and safety of novel Mycobacterium tuberculosis fusion strain protein derivatives,referred to as B/R strain active proteins.In cellular experiments,RAW264.7 cells were treated with each vaccine preparation,and apoptosis rates were measured.In subsequent animal experiments,C57BL/6 mice were immunized via subcutaneous injection,and their survival and body weight changes were monitored and recorded at 2,4,8,12,and 16 weeks.The lungs and spleens were harvested to calculate organ coefficients,and pathological examinations were conducted.At the eighth week of immunization,the mice were infected with high concentrations of BCG,and pathological changes in the lungs and spleens were observed 4 weeks post-infection.The apoptosis rate at 6 hours was significantly higher in the experimental group than the PBS group(P<0.05).At 12 and 24 hours,the apoptosis rate in the experimental group remained higher than that in the PBS group,although this difference was not statistically significant.After immunization,mice in all four groups exhibited normal growth patterns,as indicated by stable body weight changes.At 4 and 12 weeks post-immunization,the lung coefficients in the protein group were significantly higher than those in the PBS group at the same time points.Additionally,the lung coefficients in the BCG group were significantly elevated across all time periods(P<0.05).The spleen coefficients in the protein and BCG groups were significantly higher than those in the PBS group at 2,4,8,12,and 16 weeks,whereas the ICD B/R group showed higher spleen coefficients than the PBS group only at week 8(P<0.05).Pathological examination revealed normal lung and spleen tissues in the PBS group.However,during the 2-8 weeks immunization period,lung and spleen tissues in all experimental groups exhibited varying degrees of damage,which gradually diminished by 12-16 weeks.Notably,no tuberculosis nodules were observed in any experimental group.After infection with high concentrations of BCG,no overt pathological changes were observed on the surfaces of the lungs and spleens in any group.Microscopic examination revealed less severe pathological changes in the lungs and spleens of mice in the experimental groups than the PBS group.Furthermore,no statistically significant differences were observed between the protein group and the BCG group.Our findings suggested that the B/R strain active proteins'toxicity and safety profiles were comparable to those of BCG,and showed immunoprotective effects.This study provides an experimental foundation for the development of a novel tuberculosis vaccine.
