title: Central memory CD4+ T cells are responsible for the recombinant Bacillus Calmette-Guérin ΔureC::hly vaccine's superior protection against tuberculosis.
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.
authors.affiliation: Department of Immunology.
authors.forename: Alexis
authors.initials: A
authors.lastname: Vogelzang
authors.affiliation: Department of Immunology.
authors.forename: Carolina
authors.initials: C
authors.lastname: Perdomo
authors.affiliation: Department of Immunology.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Zedler
authors.affiliation: Department of Immunology.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kuhlmann
authors.affiliation: Core Facility Protein Purification, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Hurwitz
authors.affiliation: Department of Immunology.
authors.forename: Martin
authors.initials: M
authors.lastname: Gengenbacher
authors.affiliation: Department of Immunology.
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D017353:Gene Deletion; D007156:Immunologic Memory; D008297:Male; D008810:Mice, Inbred C57BL; D016254:Mutagenesis, Insertional; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D014376:Tuberculosis / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D001500:BCG Vaccine; D014614:Vaccines, Synthetic
keywords: BCG; Mycobacterium tuberculosis; VPM1002; memory T cells; vaccine; ΔureC::hly