Central memory CD4+ T cells are responsible for the recombinant Bacillus Calmette-Guérin ΔureC::hly vaccine's superior protection against tuberculosis

Alexis Vogelzang; Carolina Perdomo; Ulrike Zedler; Stefanie Kuhlmann; Robert Hurwitz; Martin Gengenbacher; Stefan H.E. Kaufmann

doi:10.1093/infdis/jiu347

Central memory CD4⁺ T cells are responsible for the recombinant Bacillus Calmette-Guérin ΔureC::hly vaccine's superior protection against tuberculosis

Alexis Vogelzang
, Carolina Perdomo
, Ulrike Zedler
, Stefanie Kuhlmann
, Robert Hurwitz
, Martin Gengenbacher
, Stefan H.E. Kaufmann

Center for Discovery and Innovation

Hackensack Meridian School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Bacillus Calmette-Guérin (BCG) has been used for vaccination against tuberculosis for nearly a century. Here, we analyze immunity induced by a live tuberculosis vaccine candidate, recombinant BCG ΔureC::hly vaccine (rBCG), with proven preclinical and clinical safety and immunogenicity. We pursue in-depth analysis of the endogenous mycobacteria-specific CD4⁺ T-cell population, comparing the more efficacious rBCG with canonical BCG to determine which T-cell memory responses are prerequisites for superior protection against tuberculosis. rBCG induced higher numbers and proportions of antigen-specific memory CD4⁺ T cells than BCG, with a CXCR5⁺ CCR7⁺ phenotype and low expression of the effector transcription factors T-bet and Bcl-6. We found that the superior protection of rBCG, compared with BCG, correlated with higher proportions and numbers of these central memory T cells and of T follicular helper cells associated with specific antibody responses. Adoptive transfer of mycobacteria-specific central memory T cells validated their critical role in protection against pulmonary tuberculosis.

Original language	English
Pages (from-to)	1928-1937
Number of pages	10
Journal	Journal of Infectious Diseases
Volume	210
Issue number	12
DOIs	https://doi.org/10.1093/infdis/jiu347
State	Published - Dec 2014

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

General Medicine

Keywords

BCG
Memory T cells
Mycobacterium tuberculosis
VPM1002
Vaccine
ΔureC::hly

Access to Document

10.1093/infdis/jiu347

Cite this

@article{360ecb6ef202442e8208643adebe93ac,

title = "Central memory CD4+ T cells are responsible for the recombinant Bacillus Calmette-Gu{\'e}rin ΔureC::hly vaccine's superior protection against tuberculosis",

abstract = "Bacillus Calmette-Gu{\'e}rin (BCG) has been used for vaccination against tuberculosis for nearly a century. Here, we analyze immunity induced by a live tuberculosis vaccine candidate, recombinant BCG ΔureC::hly vaccine (rBCG), with proven preclinical and clinical safety and immunogenicity. We pursue in-depth analysis of the endogenous mycobacteria-specific CD4+ T-cell population, comparing the more efficacious rBCG with canonical BCG to determine which T-cell memory responses are prerequisites for superior protection against tuberculosis. rBCG induced higher numbers and proportions of antigen-specific memory CD4+ T cells than BCG, with a CXCR5+ CCR7+ phenotype and low expression of the effector transcription factors T-bet and Bcl-6. We found that the superior protection of rBCG, compared with BCG, correlated with higher proportions and numbers of these central memory T cells and of T follicular helper cells associated with specific antibody responses. Adoptive transfer of mycobacteria-specific central memory T cells validated their critical role in protection against pulmonary tuberculosis.",

keywords = "BCG, Memory T cells, Mycobacterium tuberculosis, VPM1002, Vaccine, ΔureC::hly",

author = "Alexis Vogelzang and Carolina Perdomo and Ulrike Zedler and Stefanie Kuhlmann and Robert Hurwitz and Martin Gengenbacher and Kaufmann, \{Stefan H.E.\}",

note = "Publisher Copyright: {\textcopyright} The Author 2014.",

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AU - Vogelzang, Alexis

AU - Perdomo, Carolina

AU - Zedler, Ulrike

AU - Kuhlmann, Stefanie

AU - Hurwitz, Robert

AU - Gengenbacher, Martin

AU - Kaufmann, Stefan H.E.

N1 - Publisher Copyright: © The Author 2014.

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N2 - Bacillus Calmette-Guérin (BCG) has been used for vaccination against tuberculosis for nearly a century. Here, we analyze immunity induced by a live tuberculosis vaccine candidate, recombinant BCG ΔureC::hly vaccine (rBCG), with proven preclinical and clinical safety and immunogenicity. We pursue in-depth analysis of the endogenous mycobacteria-specific CD4+ T-cell population, comparing the more efficacious rBCG with canonical BCG to determine which T-cell memory responses are prerequisites for superior protection against tuberculosis. rBCG induced higher numbers and proportions of antigen-specific memory CD4+ T cells than BCG, with a CXCR5+ CCR7+ phenotype and low expression of the effector transcription factors T-bet and Bcl-6. We found that the superior protection of rBCG, compared with BCG, correlated with higher proportions and numbers of these central memory T cells and of T follicular helper cells associated with specific antibody responses. Adoptive transfer of mycobacteria-specific central memory T cells validated their critical role in protection against pulmonary tuberculosis.

AB - Bacillus Calmette-Guérin (BCG) has been used for vaccination against tuberculosis for nearly a century. Here, we analyze immunity induced by a live tuberculosis vaccine candidate, recombinant BCG ΔureC::hly vaccine (rBCG), with proven preclinical and clinical safety and immunogenicity. We pursue in-depth analysis of the endogenous mycobacteria-specific CD4+ T-cell population, comparing the more efficacious rBCG with canonical BCG to determine which T-cell memory responses are prerequisites for superior protection against tuberculosis. rBCG induced higher numbers and proportions of antigen-specific memory CD4+ T cells than BCG, with a CXCR5+ CCR7+ phenotype and low expression of the effector transcription factors T-bet and Bcl-6. We found that the superior protection of rBCG, compared with BCG, correlated with higher proportions and numbers of these central memory T cells and of T follicular helper cells associated with specific antibody responses. Adoptive transfer of mycobacteria-specific central memory T cells validated their critical role in protection against pulmonary tuberculosis.

KW - BCG

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KW - Vaccine

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