Limits...
A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis.

da Costa AC, Costa-Júnior Ade O, de Oliveira FM, Nogueira SV, Rosa JD, Resende DP, Kipnis A, Junqueira-Kipnis AP - PLoS ONE (2014)

Bottom Line: Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG.Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load.In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunopatologia das Doenças Infecciosas, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.

ABSTRACT
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials.

Show MeSH

Related in: MedlinePlus

Representative lung pathology of Balb/c mice after challenge.Vaccinated mice were challenged i.v. with 105 CFU of virulent M. tuberculosis H37Rv strain. Forty-five days after infection, lung tissue sections from different vaccine groups were harvested. Images are representative of two distinct experiments. HE staining is shown with 20X magnification. (A) Unvaccinated group. Black arrowheads: Foamy macrophages. (B) BCG-vaccinated group. (C) rBCG-CMX vaccinated group. (D) Histological score of the lesion area from three representative fields obtained by AxioVision 4.9.1 software, through ratio of lesioned and total field area. Data are presented as percentages (%).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4232451&req=5

pone-0112848-g009: Representative lung pathology of Balb/c mice after challenge.Vaccinated mice were challenged i.v. with 105 CFU of virulent M. tuberculosis H37Rv strain. Forty-five days after infection, lung tissue sections from different vaccine groups were harvested. Images are representative of two distinct experiments. HE staining is shown with 20X magnification. (A) Unvaccinated group. Black arrowheads: Foamy macrophages. (B) BCG-vaccinated group. (C) rBCG-CMX vaccinated group. (D) Histological score of the lesion area from three representative fields obtained by AxioVision 4.9.1 software, through ratio of lesioned and total field area. Data are presented as percentages (%).

Mentions: Lung architecture preservation is yet another important aspect of a successful vaccine against TB. Histological analysis of the lungs of vaccinated mice challenged with Mtb showed that 45 days after challenge, unimmunized mice had intensive lymphocytic and neutrophilic infiltrates, significantly compromising the lung tissue architecture, together with the presence of a few hemorrhagic foci and foamy macrophages (Fig. 9A). BCG-vaccinated mice, instead, showed significantly fewer lung lesions, with a preservation of alveolar spaces and very limited lymphocytic infiltrate foci (Fig. 9B). The recombinant vaccine greatly preserved the lung architecture, showing very few inflammatory infiltrates (Fig. 9C). Similar results were obtained for animals immunized with rBCG-CMX and boosted with rCMX (Data not shown). The differences in inflammatory responses upon Mtb challenge between all three groups are summarized in the scores of their lung lesions, which are presented in Figure 9D.


A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis.

da Costa AC, Costa-Júnior Ade O, de Oliveira FM, Nogueira SV, Rosa JD, Resende DP, Kipnis A, Junqueira-Kipnis AP - PLoS ONE (2014)

Representative lung pathology of Balb/c mice after challenge.Vaccinated mice were challenged i.v. with 105 CFU of virulent M. tuberculosis H37Rv strain. Forty-five days after infection, lung tissue sections from different vaccine groups were harvested. Images are representative of two distinct experiments. HE staining is shown with 20X magnification. (A) Unvaccinated group. Black arrowheads: Foamy macrophages. (B) BCG-vaccinated group. (C) rBCG-CMX vaccinated group. (D) Histological score of the lesion area from three representative fields obtained by AxioVision 4.9.1 software, through ratio of lesioned and total field area. Data are presented as percentages (%).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232451&req=5

pone-0112848-g009: Representative lung pathology of Balb/c mice after challenge.Vaccinated mice were challenged i.v. with 105 CFU of virulent M. tuberculosis H37Rv strain. Forty-five days after infection, lung tissue sections from different vaccine groups were harvested. Images are representative of two distinct experiments. HE staining is shown with 20X magnification. (A) Unvaccinated group. Black arrowheads: Foamy macrophages. (B) BCG-vaccinated group. (C) rBCG-CMX vaccinated group. (D) Histological score of the lesion area from three representative fields obtained by AxioVision 4.9.1 software, through ratio of lesioned and total field area. Data are presented as percentages (%).
Mentions: Lung architecture preservation is yet another important aspect of a successful vaccine against TB. Histological analysis of the lungs of vaccinated mice challenged with Mtb showed that 45 days after challenge, unimmunized mice had intensive lymphocytic and neutrophilic infiltrates, significantly compromising the lung tissue architecture, together with the presence of a few hemorrhagic foci and foamy macrophages (Fig. 9A). BCG-vaccinated mice, instead, showed significantly fewer lung lesions, with a preservation of alveolar spaces and very limited lymphocytic infiltrate foci (Fig. 9B). The recombinant vaccine greatly preserved the lung architecture, showing very few inflammatory infiltrates (Fig. 9C). Similar results were obtained for animals immunized with rBCG-CMX and boosted with rCMX (Data not shown). The differences in inflammatory responses upon Mtb challenge between all three groups are summarized in the scores of their lung lesions, which are presented in Figure 9D.

Bottom Line: Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG.Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load.In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunopatologia das Doenças Infecciosas, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.

ABSTRACT
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials.

Show MeSH
Related in: MedlinePlus