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Recombinant HBHA boosting effect on BCG-induced immunity against Mycobacterium tuberculosis infection.

Guerrero GG, Locht C - Clin. Dev. Immunol. (2011)

Bottom Line: However, nHBHA is characterized by a complex methylation pattern in its C-terminal domain, which is important for protective immunogenicity in primary vaccination.We found that while subcutaneous rHBHA boosting enhanced protection of BCG-primed mice against intranasal M. tuberculosis infection both in spleen and lungs, enhanced protection against aerosol infection was only seen in the spleen (0.72 logs; P < 0.05) but not in the lungs.This report thus provides evidence that rHBHA may be considered as a booster vaccine against disseminated tuberculosis.

View Article: PubMed Central - PubMed

Affiliation: INSERM U1019, Lille, France. gloriaguillermina@correo.unam.mx

ABSTRACT
Heterologous prime-boost regimens are effective strategies to promote long-term memory and strong cellular Th1 responses to Mycobacterium tuberculosis, when BCG is used in the priming step. Subcutaneous or intranasal boosting of BCG-vaccinated newborn mice with native heparin-binding haemagglutinin (nHBHA) significantly enhances protection against M. tuberculosis. However, nHBHA is characterized by a complex methylation pattern in its C-terminal domain, which is important for protective immunogenicity in primary vaccination. In this study we addressed the question whether boosting with recombinant, non-methylated HBHA (rHBHA) produced in Escherichia coli may enhance protection of BCG-primed newborn mice. We found that while subcutaneous rHBHA boosting enhanced protection of BCG-primed mice against intranasal M. tuberculosis infection both in spleen and lungs, enhanced protection against aerosol infection was only seen in the spleen (0.72 logs; P < 0.05) but not in the lungs. Thus, in BCG-primed mice the methylation of the C-terminal domain of HBHA is dispensable for the induction of enhanced protection in the lungs against intranasal but not aerosol infection, whereas it enhances protection in the spleen in both challenge models. This report thus provides evidence that rHBHA may be considered as a booster vaccine against disseminated tuberculosis.

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Related in: MedlinePlus

Lung cell cytokine profile of BCG-vaccinated mice with or without rHBHA boost after M. tuberculosis infection. Eight weeks after i.n. (A) or aerosol (B) challenge lung cells from control mice (white bars), BCG-vaccinated mice (black bars), or BCG-vaccinated/rHBHA-boosted mice (gray bars) were cultured in the presence of medium only, ConA (2.5 μg/mL), or rHBHA (5 μg/mL). Levels of cytokines were measured after 72 h culture in the supernatants by using the OptEIA kit (BD Biosciences). Values are expressed in pg/mL and represent media ± SEM of samples tested in duplicates from each group of mice. Statistically significant data: P < 0.05 (*), P < 0.001 (**), and P < 0.0001 (***).
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fig2: Lung cell cytokine profile of BCG-vaccinated mice with or without rHBHA boost after M. tuberculosis infection. Eight weeks after i.n. (A) or aerosol (B) challenge lung cells from control mice (white bars), BCG-vaccinated mice (black bars), or BCG-vaccinated/rHBHA-boosted mice (gray bars) were cultured in the presence of medium only, ConA (2.5 μg/mL), or rHBHA (5 μg/mL). Levels of cytokines were measured after 72 h culture in the supernatants by using the OptEIA kit (BD Biosciences). Values are expressed in pg/mL and represent media ± SEM of samples tested in duplicates from each group of mice. Statistically significant data: P < 0.05 (*), P < 0.001 (**), and P < 0.0001 (***).

Mentions: Lung cell IL-12 production of BCG-vaccinated/rHBHA-boosted mice infected i.n. was significantly higher (3800 ± 560 pg/mL) (Figure 2A) than that of non-boosted mice (2280 ± 335 pg/mL) or PBS control mice (433 ± 222 pg/mL) (Figure 2A). Interestingly, the lung cells from BCG-vaccinated/rHBHA-boosted mice also produced higher amounts of TGF-β (2240 ± 290 pg/mL) after i.n. infection, in comparison with non-boosted mice (1707 ± 122 pg/mL) and the controls (489 ± 277). The lung cell IL-10 production was significantly higher in BCG-vaccinated/rHBHA-boosted mice (1955 ± 275 pg/mL) than in non-boosted (252 ± 42 pg/mL) and in control mice (68 ± 7 pg/mL) after i.n. infection (Figure 2A). Very low levels of IFN-γ were produced by lung cells in all three groups (Figure 2A). The lung cell IL-6 and IL-17 production was higher in the BCG-vaccinated non-boosted mice (451 ± 33 pg/mL) than in the BCG-vaccinated/rHBHA-boosted (271 ± 37) and in the PBS control mice (133 ± 7 pg/mL) after i.n. infection. No difference in lung cell IL-17 production between boosted and non-boosted mice was seen (Figure 2A).


Recombinant HBHA boosting effect on BCG-induced immunity against Mycobacterium tuberculosis infection.

Guerrero GG, Locht C - Clin. Dev. Immunol. (2011)

Lung cell cytokine profile of BCG-vaccinated mice with or without rHBHA boost after M. tuberculosis infection. Eight weeks after i.n. (A) or aerosol (B) challenge lung cells from control mice (white bars), BCG-vaccinated mice (black bars), or BCG-vaccinated/rHBHA-boosted mice (gray bars) were cultured in the presence of medium only, ConA (2.5 μg/mL), or rHBHA (5 μg/mL). Levels of cytokines were measured after 72 h culture in the supernatants by using the OptEIA kit (BD Biosciences). Values are expressed in pg/mL and represent media ± SEM of samples tested in duplicates from each group of mice. Statistically significant data: P < 0.05 (*), P < 0.001 (**), and P < 0.0001 (***).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3102518&req=5

fig2: Lung cell cytokine profile of BCG-vaccinated mice with or without rHBHA boost after M. tuberculosis infection. Eight weeks after i.n. (A) or aerosol (B) challenge lung cells from control mice (white bars), BCG-vaccinated mice (black bars), or BCG-vaccinated/rHBHA-boosted mice (gray bars) were cultured in the presence of medium only, ConA (2.5 μg/mL), or rHBHA (5 μg/mL). Levels of cytokines were measured after 72 h culture in the supernatants by using the OptEIA kit (BD Biosciences). Values are expressed in pg/mL and represent media ± SEM of samples tested in duplicates from each group of mice. Statistically significant data: P < 0.05 (*), P < 0.001 (**), and P < 0.0001 (***).
Mentions: Lung cell IL-12 production of BCG-vaccinated/rHBHA-boosted mice infected i.n. was significantly higher (3800 ± 560 pg/mL) (Figure 2A) than that of non-boosted mice (2280 ± 335 pg/mL) or PBS control mice (433 ± 222 pg/mL) (Figure 2A). Interestingly, the lung cells from BCG-vaccinated/rHBHA-boosted mice also produced higher amounts of TGF-β (2240 ± 290 pg/mL) after i.n. infection, in comparison with non-boosted mice (1707 ± 122 pg/mL) and the controls (489 ± 277). The lung cell IL-10 production was significantly higher in BCG-vaccinated/rHBHA-boosted mice (1955 ± 275 pg/mL) than in non-boosted (252 ± 42 pg/mL) and in control mice (68 ± 7 pg/mL) after i.n. infection (Figure 2A). Very low levels of IFN-γ were produced by lung cells in all three groups (Figure 2A). The lung cell IL-6 and IL-17 production was higher in the BCG-vaccinated non-boosted mice (451 ± 33 pg/mL) than in the BCG-vaccinated/rHBHA-boosted (271 ± 37) and in the PBS control mice (133 ± 7 pg/mL) after i.n. infection. No difference in lung cell IL-17 production between boosted and non-boosted mice was seen (Figure 2A).

Bottom Line: However, nHBHA is characterized by a complex methylation pattern in its C-terminal domain, which is important for protective immunogenicity in primary vaccination.We found that while subcutaneous rHBHA boosting enhanced protection of BCG-primed mice against intranasal M. tuberculosis infection both in spleen and lungs, enhanced protection against aerosol infection was only seen in the spleen (0.72 logs; P < 0.05) but not in the lungs.This report thus provides evidence that rHBHA may be considered as a booster vaccine against disseminated tuberculosis.

View Article: PubMed Central - PubMed

Affiliation: INSERM U1019, Lille, France. gloriaguillermina@correo.unam.mx

ABSTRACT
Heterologous prime-boost regimens are effective strategies to promote long-term memory and strong cellular Th1 responses to Mycobacterium tuberculosis, when BCG is used in the priming step. Subcutaneous or intranasal boosting of BCG-vaccinated newborn mice with native heparin-binding haemagglutinin (nHBHA) significantly enhances protection against M. tuberculosis. However, nHBHA is characterized by a complex methylation pattern in its C-terminal domain, which is important for protective immunogenicity in primary vaccination. In this study we addressed the question whether boosting with recombinant, non-methylated HBHA (rHBHA) produced in Escherichia coli may enhance protection of BCG-primed newborn mice. We found that while subcutaneous rHBHA boosting enhanced protection of BCG-primed mice against intranasal M. tuberculosis infection both in spleen and lungs, enhanced protection against aerosol infection was only seen in the spleen (0.72 logs; P < 0.05) but not in the lungs. Thus, in BCG-primed mice the methylation of the C-terminal domain of HBHA is dispensable for the induction of enhanced protection in the lungs against intranasal but not aerosol infection, whereas it enhances protection in the spleen in both challenge models. This report thus provides evidence that rHBHA may be considered as a booster vaccine against disseminated tuberculosis.

Show MeSH
Related in: MedlinePlus