Evaluation of protective efficacy conferred by a recombinant Mycobacterium bovis BCG expressing a fusion protein of Ag85A-ESAT-6.
BACKGROUND
We previously constructed a recombinant bacille Calmette-Guérin (rBCG-AE) strain that could express a fused Ag85A-ESAT-6 protein. That study suggested that the rBCG-AE strain was able to induce a higher titer of antibody and elicit a more long-lived and stronger Th1-type cellular immune responses than the parental BCG strain, the rBCG-A strain (i.e., expressing Ag85A), or the rBCG-E strain (i.e., expressing ESAT-6).


METHODS
In the current study, we further investigated the strain's protective efficacy against Mycobacterium tuberculosis H37Rv infection in BALB/c mice through evaluating organ bacterial loads, lung histopathology, lung immunohistochemistry, and net weight gain or loss by using conventional BCG, rBCG-A, and rBCG-E as the controls.


RESULTS
From the 3rd to 9th weeks after the challenge infection, the bacterial counts were significantly lower in tissues (e.g., spleen and lung tissues) in the mice immunized with rBCG-AE than in the control group, but were higher than the counts in the BCG group. The pathological damage in the lung tissues of the rBCG-AE group gradually improved from the 6th to 9th weeks after being infected with M. tuberculosis H37Rv, but the score of pathological changes in the rBCG-AE group was obviously higher than the score in the BCG group. There was no difference in the percentage of IFN-γ and iNOS positive cells in the lung tissues of the rBCG-AE and BCG groups.


CONCLUSIONS
The results suggest that rBCG-AE can not promote protective efficacy against M. tuberculosis H37Rv infection, compared to the BCG vaccine.
Department of Human Anatomy, College of Preclinical Medicine, Dali University, Dali 671000, China. Electronic address: deng13032871868@163.com.
Yi-Hao
YH
Deng
Department of Human Anatomy, College of Preclinical Medicine, Dali University, Dali 671000, China.
Hong-Yun
HY
He
Department of Human Anatomy, College of Preclinical Medicine, Dali University, Dali 671000, China.
Ben-Si
BS
Zhang
D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001835:Body Weight; D005260:Female; D006651:Histocytochemistry; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000302:isolation & purification; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis
Ag85A; ESAT-6; Protective efficacy; Recombinant Mycobacterium bovis bacillus Calmette-Guérin (rBCG)