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Assessment of Immune Protective T Cell Repertoire in Humans Immunized with Novel Tuberculosis Vaccines

  • Mangalakumari Jeyanathan
  • Zhou XingEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2111)

Abstract

Tuberculosis (TB) is one of the major global health concerns. There has been a lack of an effective vaccine strategy. The Bacillus Calmette-Guerin (BCG), the only licensed vaccine against TB, is not effective against adult pulmonary TB, the highly contagious form of TB. In the past two decades or so, many novel TB vaccines have been developed, and some of them were evaluated in clinical trials. However, the lack of validated immune correlates to assess the clinical relevance of novel TB vaccines before their entry into costly efficacy trials is a huge challenge to the field of TB vaccine development. Here we describe a general protocol for the procedure of a systematic immunological approach that can be utilized to better assess the clinical relevance of TB vaccine-activated T cells in early phases of clinical studies.

Key words

Tuberculosis Mycobacteria Ad5Ag85A Peptide Epitope PBMC Ag-specific T cell line MGIA 

Notes

Acknowledgments

The work is supported by funds from the Foundation Program of the Canadian Institutes of Health Research (CIHR) and the Collaborative Health Research Program of CIHR and the Natural Sciences and Engineering Research Council of Canada.

References

  1. 1.
    WHO (2018) Global tuberculosis report. WHO, GenevaGoogle Scholar
  2. 2.
    Voss G, Casimiro D, Neyrolles O et al (2018) Progress and challenges in TB vaccine development. F1000Res 7:199CrossRefGoogle Scholar
  3. 3.
    Kaufmann SHE, Dockrell HM, Drager N et al (2017) TBVAC2020: advancing tuberculosis vaccines from discovery to clinical development. Front Immunol 8:1203.  https://doi.org/10.3389/fimmu.2017.01203CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Xing Z, Jeyanathan M, Smaill F (2014) New approaches to TB vaccination. Chest 146:804–812CrossRefGoogle Scholar
  5. 5.
    Tameris MD, Hatherill M, Landry BS et al (2013) Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet 381:1021–1028CrossRefGoogle Scholar
  6. 6.
    Nemes E, Geldenhuys H, Rozot V et al (2018) Prevention of M. tuberculosis infection with H4:IC31 vaccine or BCG revaccination. N Engl J Med 379:138–149CrossRefGoogle Scholar
  7. 7.
    Kaufmann SHE, Weiner J, von Reyn CF (2017) Novel approaches to tuberculosis vaccine development. Int J Infect Dis 56:263–267CrossRefGoogle Scholar
  8. 8.
    Jeyanathan M, Yao Y, Afkhami S et al (2018) New tuberculosis vaccine strategies: taking aim at un-natural immunity. Trends Immunol 39:419–433CrossRefGoogle Scholar
  9. 9.
    Li Q, Song H-Y, Ellner JJ et al (2002) Bactericidal activity in whole blood as a potential surrogate marker of immunity after vaccination against tuberculosis. Clin Vaccine Immunol 9:901–907CrossRefGoogle Scholar
  10. 10.
    Li Q, Hoft DF, Kampmann B et al (2002) Investigation of the relationships between immune-mediated inhibition of Mycobacterial growth and other potential surrogate markers of protective Mycobacterium tuberculosis immunity. J Infect Dis 186:1448–1457CrossRefGoogle Scholar
  11. 11.
    Minassian AM, Satti I, Poulton ID et al (2012) A human challenge model for Mycobacterium tuberculosis using Mycobacterium bovis bacille Calmette-Guérin. J Infect Dis 205:1035–1042CrossRefGoogle Scholar
  12. 12.
    Jeyanathan M, Damjanovic D, Yao Y et al (2016) Induction of an immune-protective t-cell repertoire with diverse genetic coverage by a novel viral-vectored tuberculosis vaccine in humans. J Infect Dis 214:1996–2005CrossRefGoogle Scholar
  13. 13.
    Hoffmeister B, Kiecker F, Tesfa L et al (2003) Mapping T cell epitopes by flow cytometry. Methods 29:270–281CrossRefGoogle Scholar
  14. 14.
    Peters B, Sette A, Kim Y et al (2012) Immune epitope database analysis resource. Nucleic Acids Res 40:W525–W530CrossRefGoogle Scholar
  15. 15.
    Weichold FF, Mueller S, Kortsik C et al (2007) Impact of MHC class I alleles on the M. tuberculosis antigen-specific CD8+ T-cell response in patients with pulmonary tuberculosis. Genes Immun 8:334–343CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of Pathology and Molecular Medicine, McMaster Immunology Research CentreMcMaster UniversityHamiltonCanada
  2. 2.Michael G. DeGroote Institute for Infectious Disease ResearchMcMaster UniversityHamiltonCanada

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