In-vivo expressed Mycobacterium tuberculosis antigens recognised in three mouse strains after infection and BCG vaccination

Coppola, Mariateresa; Jurion, Fabienne; Eeden, Susan J. F. van den; Tima, Hermann Giresse; Franken, Kees L. M. C.; Geluk, Annemieke; Romano, Márta; Ottenhoff, Tom H. M.

doi:10.1038/s41541-021-00343-2

Cited by 10 publications

(8 citation statements)

References 49 publications

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Section: Previously We Reported That a Hygromycin Resistant Version O...mentioning

confidence: 99%

“…Bacillus Calmette-Guerin (BCG), the only currently licenced vaccine against TB, confer insufficient protection in adolescents and adults against pulmonary TB 4 . Therefore, numerous efforts have aimed to develop improved TB vaccines in recent decades by employing strategies surveying genes expressed in vivo [5][6][7] .To overcome the insufficient protection mediated by BCG, over 20 novel TB vaccine candidates through diverse strategies involving recombinant live mycobacterial vaccines and boosting BCG with subunit vaccines…”

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confidence: 99%

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BCGΔBCG1419c increased memory CD8+ T cell-associated immunogenicity and mitigated pulmonary inflammation compared with BCG in a model of chronic tuberculosis

Kwon

Aceves-Sánchez

Segura-Cerda

et al. 2022

Sci Rep

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Previously, we reported that a hygromycin resistant version of the BCGΔBCG1419c vaccine candidate reduced tuberculosis (TB) disease in BALB/c, C57BL/6, and B6D2F1 mice infected with Mycobacterium tuberculosis (Mtb) H37Rv. Here, the second-generation version of BCGΔBCG1419c (based on BCG Pasteur ATCC 35734, without antibiotic resistance markers, and a complete deletion of BCG1419c) was compared to its parental BCG for immunogenicity and protective efficacy against the Mtb clinical isolate M2 in C57BL/6 mice. Both BCG and BCGΔBCG1419c induced production of IFN-γ, TNF-α, and/or IL-2 by effector memory (CD44+CD62L−), PPD-specific, CD4+ T cells, and only BCGΔBCG1419c increased effector memory, PPD-specific CD8+ T cell responses in the lungs and spleens compared with unvaccinated mice before challenge. BCGΔBCG1419c increased levels of central memory (CD62L+CD44+) T CD4+ and CD8+ cells compared to those of BCG-vaccinated mice. Both BCG strains elicited Th1-biased antigen-specific polyfunctional effector memory CD4+/CD8+ T cell responses at 10 weeks post-infection, and both vaccines controlled Mtb M2 growth in the lung and spleen. Only BCGΔBCG1419c significantly ameliorated pulmonary inflammation and decreased neutrophil infiltration into the lung compared to BCG-vaccinated and unvaccinated mice. Both BCG strains reduced pulmonary TNF-α, IFN-γ, and IL-10 levels. Taken together, BCGΔBCG1419c increased memory CD8+T cell-associated immunogenicity and mitigated pulmonary inflammation compared with BCG.

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Section: Previously We Reported That a Hygromycin Resistant Version O...mentioning

confidence: 99%

mentioning

confidence: 99%

BCGΔBCG1419c increased memory CD8+ T cell-associated immunogenicity and mitigated pulmonary inflammation compared with BCG in a model of chronic tuberculosis

Kwon

Aceves-Sánchez

Segura-Cerda

et al. 2022

Sci Rep

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“…This is likely due to one or both of the following reasons: (1) Mtb infected lungs already contain an array of immune innate lineages which restrict CoV2, or (2) Mtb elicits an adaptive immune response that cross reacts with CoV2 antigens and offers heterologous immunity. This latter explanation is supported by recent epidemiological studies of COVID among individuals vaccinated with M. bovis BCG[17][18][19], which depending on the strain has significant antigenic overlap with Mtb[20,21].…”

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confidence: 71%

Mice infected with Mycobacterium tuberculosis are resistant to secondary infection with SARS-CoV-2

Mejia

Gloag

et al. 2021

Preprint

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Mycobacterium tuberculosis (Mtb) and SARS-CoV-2 (CoV2) are the leading causes of death due to infectious disease. Although Mtb and CoV2 both cause serious and sometimes fatal respiratory infections, the effect of Mtb infection and its associated immune response on secondary infection with CoV2 is unknown. To address this question we applied two mouse models of COVID19, using mice which were chronically infected with Mtb. In both model systems, Mtb-infected mice were resistant to secondary CoV2 infection and its pathological consequences, and CoV2 infection did not affect Mtb burdens. Single cell RNA sequencing of coinfected and monoinfected lungs demonstrated the resistance of Mtb-infected mice is associated with expansion of T and B cell subsets upon viral challenge. Collectively, these data demonstrate that Mtb infection conditions the lung environment in a manner that is not conducive to CoV2 survival.AUTHOR SUMMARYMycobacterium tuberculosis (Mtb) and SARS-CoV-2 (CoV2) are distinct organisms which both cause lung disease. We report the surprising observation that Mtb-infected mice are resistant to secondary infection with CoV2, with no impact on Mtb burden and resistance associating with lung T and B cell expansion.

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“…T cell responses at the antigen and epitope levels are highly complex, particularly in complex organisms. They can involve multiple antigens and hundreds of epitopes (22)(23)(24)(25), with broader patterns of immunodominance observed in humans compared to genetically homogeneous murine model (26)(27)(28). While the mechanisms underlying T cell immunodominance and breadth have been extensively studied in murine models and, to some extent, in humans (22,(29)(30)(31) (32), a quantitative assessment of the complexity of responses during natural infections at the population level is currently lacking.…”

Section: T Cells Are Critical In the Host Immune Response Against Mtb...mentioning

confidence: 99%

Identification of differentially recognized T cell epitopes in the spectrum ofMtbinfection

Panda

Morgan

Cheng

et al. 2023

Preprint

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Tuberculosis caused by Mycobacterium tuberculosis is one of the leading causes of death from a single infectious agent. Identifying dominant epitopes and comparing their reactivity in different tuberculosis (TB) infection states can help design diagnostics and vaccines. We performed a proteome-wide screen of 20,610 Mtb derived peptides in 21 Active TB (ATB) patients 3-4 months post-diagnosis of pulmonary TB (mid-treatment) using an IFNgamma and IL-17 Fluorospot assay. Responses were mediated exclusively by IFNgamma and identified a total of 137 unique epitopes, with each patient recognizing, on average, 8 individual epitopes and 22 epitopes (16%) recognized by 2 or more participants. Responses were predominantly directed against antigens part of the cell wall and cell processes category. Testing 517 peptides spanning TB vaccine candidates and ESAT-6 and CFP10 antigens also revealed differential recognition between ATB participants mid-treatment and healthy IGRA+ participants of several vaccine antigens. An ATB-specific peptide pool consisting of epitopes exclusively recognized by participants mid-treatment, allowed distinguishing participants with active pulmonary TB from healthy interferon-gamma release assay (IGRA)+/- participants from diverse geographical locations. Analysis of longitudinal samples indicated decreased reactivity during treatment for pulmonary TB. Together, these results show that a proteome-wide screen of T cell reactivity identifies epitopes and antigens that are differentially recognized depending on the Mtb infection stage. These have potential use in developing diagnostics and vaccine candidates and measuring correlates of protection.

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In-vivo expressed Mycobacterium tuberculosis antigens recognised in three mouse strains after infection and BCG vaccination

Cited by 10 publications

References 49 publications

BCGΔBCG1419c increased memory CD8+ T cell-associated immunogenicity and mitigated pulmonary inflammation compared with BCG in a model of chronic tuberculosis

BCGΔBCG1419c increased memory CD8+ T cell-associated immunogenicity and mitigated pulmonary inflammation compared with BCG in a model of chronic tuberculosis

Mice infected with Mycobacterium tuberculosis are resistant to secondary infection with SARS-CoV-2

Identification of differentially recognized T cell epitopes in the spectrum ofMtbinfection

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