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Mycobacterial membrane vesicles administered systemically in mice induce a protective immune response to surface compartments of Mycobacterium tuberculosis.

Prados-Rosales R, Carreño LJ, Batista-Gonzalez A, Baena A, Venkataswamy MM, Xu J, Yu X, Wallstrom G, Magee DM, LaBaer J, Achkar JM, Jacobs WR, Chan J, Porcelli SA, Casadevall A - MBio (2014)

Bottom Line: Clin.In this work, we analyzed the vaccine potential of MV in a mouse model and compared the effects of immunization with MV to those of standard BCG vaccination.The fact that MV do not need adjuvants and elicit protection comparable to that elicited by the BCG vaccine encourages vaccine approaches that combine protein antigens and lipids.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, USA rafael.prados-rosales@einstein.yu.edu.

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Immunization with mycobacterial MV protects mice against M. tuberculosis aerosol infection. (A) Bacterial load (CFU) in the lungs of individual C57BL/6 mice, immunized SC with 1 × 106 BCG bacteria or twice SC with 2.5 µg BCG or H37Rv MV was determined at 8 weeks after infection with a low dose of M. tuberculosis H37Rv via aerosol (approximately 100 CFU). The results of three independent experiments are shown. Experimental groups used 5 mice (values labeled “a” are statistically significantly different from those labeled “b” [P < 0.05] or “c” [P < 0.01] using one-way ANOVA). (B) Representative H&E staining images from lungs of C57BL/6 mice SC immunized with BCG or with MV from BCG or H37Rv and infected with M. tuberculosis for 8 weeks. All the images were taken at a magnification of ×2.5. (C) The size of lung lesions was determined from H&E-stained cross sections using computer-assisted image analysis. These data were used to calculate the percentage area of lung tissue occupied by diseased tissue. (D) The number of lesions per lung section was determined by computer-assisted image analysis as for panel C (values labeled “a” are statistically significantly different from those labeled “b” [P < 0.05] or “c” [P < 0.01]). Data are means ± SEM.
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fig4: Immunization with mycobacterial MV protects mice against M. tuberculosis aerosol infection. (A) Bacterial load (CFU) in the lungs of individual C57BL/6 mice, immunized SC with 1 × 106 BCG bacteria or twice SC with 2.5 µg BCG or H37Rv MV was determined at 8 weeks after infection with a low dose of M. tuberculosis H37Rv via aerosol (approximately 100 CFU). The results of three independent experiments are shown. Experimental groups used 5 mice (values labeled “a” are statistically significantly different from those labeled “b” [P < 0.05] or “c” [P < 0.01] using one-way ANOVA). (B) Representative H&E staining images from lungs of C57BL/6 mice SC immunized with BCG or with MV from BCG or H37Rv and infected with M. tuberculosis for 8 weeks. All the images were taken at a magnification of ×2.5. (C) The size of lung lesions was determined from H&E-stained cross sections using computer-assisted image analysis. These data were used to calculate the percentage area of lung tissue occupied by diseased tissue. (D) The number of lesions per lung section was determined by computer-assisted image analysis as for panel C (values labeled “a” are statistically significantly different from those labeled “b” [P < 0.05] or “c” [P < 0.01]). Data are means ± SEM.

Mentions: We tested whether immunization with mycobacterial MV was protective in mice against an M. tuberculosis challenge. Immunized mice were infected with approximately with 100 CFU via aerosol, 3 weeks after the last immunization. Eight weeks after infection, lung and spleen bacterial burdens were determined. Mice immunized with PBS or two million bacilli of BCG Pasteur were used as negative and positive controls, respectively (Fig. 4; also, see Fig. S3 in the supplemental material). The experiment was done three times. Two experiments showed a protective effect for H37Rv MV, comparable to that obtained with the control BCG, with a significant reduction of lung CFU relative to levels in PBS-treated mice (Fig. 4A). Of note, immunization with BCG MV was not protective in all experiments. In one experiment, we found almost no reduction in lung CFU in H37Rv MV-immunized mice, comparable to results with unvaccinated mice (PBS) (Fig. 4A). The same trend was observed when CFU were counted in spleens (see Fig. S3). Importantly, in experiments where H37Rv MV resulted in a reduced number of CFU in the spleen, similar to BCG, some mice had numbers of spleen CFU below the limit of detection (see Fig. S3). This result indicates the potential capacity of H37Rv MV to control bacterial replication and dissemination, similar to that of BCG.


Mycobacterial membrane vesicles administered systemically in mice induce a protective immune response to surface compartments of Mycobacterium tuberculosis.

Prados-Rosales R, Carreño LJ, Batista-Gonzalez A, Baena A, Venkataswamy MM, Xu J, Yu X, Wallstrom G, Magee DM, LaBaer J, Achkar JM, Jacobs WR, Chan J, Porcelli SA, Casadevall A - MBio (2014)

Immunization with mycobacterial MV protects mice against M. tuberculosis aerosol infection. (A) Bacterial load (CFU) in the lungs of individual C57BL/6 mice, immunized SC with 1 × 106 BCG bacteria or twice SC with 2.5 µg BCG or H37Rv MV was determined at 8 weeks after infection with a low dose of M. tuberculosis H37Rv via aerosol (approximately 100 CFU). The results of three independent experiments are shown. Experimental groups used 5 mice (values labeled “a” are statistically significantly different from those labeled “b” [P < 0.05] or “c” [P < 0.01] using one-way ANOVA). (B) Representative H&E staining images from lungs of C57BL/6 mice SC immunized with BCG or with MV from BCG or H37Rv and infected with M. tuberculosis for 8 weeks. All the images were taken at a magnification of ×2.5. (C) The size of lung lesions was determined from H&E-stained cross sections using computer-assisted image analysis. These data were used to calculate the percentage area of lung tissue occupied by diseased tissue. (D) The number of lesions per lung section was determined by computer-assisted image analysis as for panel C (values labeled “a” are statistically significantly different from those labeled “b” [P < 0.05] or “c” [P < 0.01]). Data are means ± SEM.
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fig4: Immunization with mycobacterial MV protects mice against M. tuberculosis aerosol infection. (A) Bacterial load (CFU) in the lungs of individual C57BL/6 mice, immunized SC with 1 × 106 BCG bacteria or twice SC with 2.5 µg BCG or H37Rv MV was determined at 8 weeks after infection with a low dose of M. tuberculosis H37Rv via aerosol (approximately 100 CFU). The results of three independent experiments are shown. Experimental groups used 5 mice (values labeled “a” are statistically significantly different from those labeled “b” [P < 0.05] or “c” [P < 0.01] using one-way ANOVA). (B) Representative H&E staining images from lungs of C57BL/6 mice SC immunized with BCG or with MV from BCG or H37Rv and infected with M. tuberculosis for 8 weeks. All the images were taken at a magnification of ×2.5. (C) The size of lung lesions was determined from H&E-stained cross sections using computer-assisted image analysis. These data were used to calculate the percentage area of lung tissue occupied by diseased tissue. (D) The number of lesions per lung section was determined by computer-assisted image analysis as for panel C (values labeled “a” are statistically significantly different from those labeled “b” [P < 0.05] or “c” [P < 0.01]). Data are means ± SEM.
Mentions: We tested whether immunization with mycobacterial MV was protective in mice against an M. tuberculosis challenge. Immunized mice were infected with approximately with 100 CFU via aerosol, 3 weeks after the last immunization. Eight weeks after infection, lung and spleen bacterial burdens were determined. Mice immunized with PBS or two million bacilli of BCG Pasteur were used as negative and positive controls, respectively (Fig. 4; also, see Fig. S3 in the supplemental material). The experiment was done three times. Two experiments showed a protective effect for H37Rv MV, comparable to that obtained with the control BCG, with a significant reduction of lung CFU relative to levels in PBS-treated mice (Fig. 4A). Of note, immunization with BCG MV was not protective in all experiments. In one experiment, we found almost no reduction in lung CFU in H37Rv MV-immunized mice, comparable to results with unvaccinated mice (PBS) (Fig. 4A). The same trend was observed when CFU were counted in spleens (see Fig. S3). Importantly, in experiments where H37Rv MV resulted in a reduced number of CFU in the spleen, similar to BCG, some mice had numbers of spleen CFU below the limit of detection (see Fig. S3). This result indicates the potential capacity of H37Rv MV to control bacterial replication and dissemination, similar to that of BCG.

Bottom Line: Clin.In this work, we analyzed the vaccine potential of MV in a mouse model and compared the effects of immunization with MV to those of standard BCG vaccination.The fact that MV do not need adjuvants and elicit protection comparable to that elicited by the BCG vaccine encourages vaccine approaches that combine protein antigens and lipids.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, USA rafael.prados-rosales@einstein.yu.edu.

Show MeSH
Related in: MedlinePlus