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4. Enhanced protection conferred by mucosal BCG vaccination associates with presence of antigen-specific lung tissue-resident PD-1+KLRG1−CD4+T cells

Author

Bull, N.C., Stylianou, E., Kaveh, D.A., Pinpathomrat, N., Pasricha, J., Harrington-Kandt, R., Garcia-Pelayo, M.C., Hogarth, P.J., and McShane, H.

Abstract

BCG, the only vaccine licensed against tuberculosis, demonstrates variable efficacy in humans. Recent preclinical studies highlight the potential for mucosal BCG vaccination to improve protection. Lung tissue-resident memory T cells reside within the parenchyma, potentially playing an important role in protective immunity to tuberculosis. We hypothesised that mucosal BCG vaccination may enhance generation of lung tissue-resident T cells, affording improved protection against Mycobacterium tuberculosis. In a mouse model, mucosal intranasal (IN) BCG vaccination conferred superior protection in the lungs compared to the systemic intradermal (ID) route. Intravascular staining allowed discrimination of lung tissue-resident CD4+T cells from those in the lung vasculature, revealing that mucosal vaccination resulted in an increased frequency of antigen-specific tissue-resident CD4+T cells compared to systemic vaccination. Tissue-resident CD4+T cells induced by mucosal BCG displayed enhanced proliferative capacity compared to lung vascular and splenic CD4+T cells. Only mucosal BCG induced antigen-specific tissue-resident T cells expressing a PD-1+KLRG1−cell-surface phenotype. These cells constitute a BCG-induced population which may be responsible for the enhanced protection observed with IN vaccination. We demonstrate that mucosal BCG vaccination significantly improves protection over systemic BCG and this correlates with a novel population of BCG-induced lung tissue-resident CD4+T cells.

Published
2019
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5. European 2--a clonal complex of Mycobacterium bovis dominant in the Iberian Peninsula.

Author

Rodriguez-Campos, S., Schurch, A.C., Dale, J., Lohan, A.J., Cunha, M.V., Botelho, A., Cruz, K. De, Boschiroli, M.L., Boniotti, M.B., Pacciarini, M., Garcia-Pelayo, M.C., Romero, B., Juan, L. de, Dominguez, L., Gordon, S.V., Soolingen, D. van, Loftus, B., Berg, S. van den, Hewinson, R.G., Aranaz, A., Smith, N.H., Rodriguez-Campos, S., Schurch, A.C., Dale, J., Lohan, A.J., Cunha, M.V., Botelho, A., Cruz, K. De, Boschiroli, M.L., Boniotti, M.B., Pacciarini, M., Garcia-Pelayo, M.C., Romero, B., Juan, L. de, Dominguez, L., Gordon, S.V., Soolingen, D. van, Loftus, B., Berg, S. van den, Hewinson, R.G., Aranaz, A., and Smith, N.H.

Abstract

1 juni 2012, Item does not contain fulltext, Mycobacterium bovis isolates from the Iberian Peninsula are dominated by strains with spoligotype patterns deleted for spacer 21. Whole-genome sequencing of three Spanish strains with spacer 21 missing in their spoligotype pattern revealed a series of SNPs and subsequent screening of a selection of these SNPs identified one in gene guaA that is specific to these strains. This group of strains from the Iberian Peninsula missing spoligotype spacer 21 represents a new clonal complex of M. bovis, defined by the SNP profile with a distinct spoligotype signature. We have named this clonal complex European 2 (Eu2) and found that it was present at low frequency in both France and Italy and absent from the British Isles.

Published
2012

6. African 2, a clonal complex of Mycobacterium bovis epidemiologically important in East Africa.

Author

Berg, S., Garcia-Pelayo, M.C., Muller, B., Hailu, E., Asiimwe, B., Kremer, K., Dale, J., Boniotti, M.B., Rodriguez, S., Hilty, M., Rigouts, L., Firdessa, R., Machado, A., Mucavele, C., Ngandolo, B.N., Bruchfeld, J., Boschiroli, L., Muller, A., Sahraoui, N., Pacciarini, M., Cadmus, S., Joloba, M., Soolingen, D. van, Michel, A.L., Djonne, B., Aranaz, A., Zinsstag, J., Helden, P. van, Portaels, F., Kazwala, R., Kallenius, G., Hewinson, R.G., Aseffa, A., Gordon, S.V., Smith, N.H., Berg, S., Garcia-Pelayo, M.C., Muller, B., Hailu, E., Asiimwe, B., Kremer, K., Dale, J., Boniotti, M.B., Rodriguez, S., Hilty, M., Rigouts, L., Firdessa, R., Machado, A., Mucavele, C., Ngandolo, B.N., Bruchfeld, J., Boschiroli, L., Muller, A., Sahraoui, N., Pacciarini, M., Cadmus, S., Joloba, M., Soolingen, D. van, Michel, A.L., Djonne, B., Aranaz, A., Zinsstag, J., Helden, P. van, Portaels, F., Kazwala, R., Kallenius, G., Hewinson, R.G., Aseffa, A., Gordon, S.V., and Smith, N.H.

Abstract

1 februari 2011, Item does not contain fulltext, We have identified a clonal complex of Mycobacterium bovis isolated at high frequency from cattle in Uganda, Burundi, Tanzania, and Ethiopia. We have named this related group of M. bovis strains the African 2 (Af2) clonal complex of M. bovis. Af2 strains are defined by a specific chromosomal deletion (RDAf2) and can be identified by the absence of spacers 3 to 7 in their spoligotype patterns. Deletion analysis of M. bovis isolates from Algeria, Mali, Chad, Nigeria, Cameroon, South Africa, and Mozambique did not identify any strains of the Af2 clonal complex, suggesting that this clonal complex of M. bovis is localized in East Africa. The specific spoligotype pattern of the Af2 clonal complex was rarely identified among isolates from outside Africa, and the few isolates that were found and tested were intact at the RDAf2 locus. We conclude that the Af2 clonal complex is localized to cattle in East Africa. We found that strains of the Af2 clonal complex of M. bovis have, in general, four or more copies of the insertion sequence IS6110, in contrast to the majority of M. bovis strains isolated from cattle, which are thought to carry only one or a few copies.

Published
2011

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