A comparison of antigen-specific T cell responses induced by six novel tuberculosis vaccine candidates

PLoS Pathogens
Miguel J RodoThomas J Scriba

Abstract

Eradication of tuberculosis (TB), the world's leading cause of death due to infectious disease, requires a highly efficacious TB vaccine. Many TB vaccine candidates are in pre-clinical and clinical development but only a few can be advanced to large-scale efficacy trials due to limited global resources. We aimed to perform a statistically rigorous comparison of the antigen-specific T cell responses induced by six novel TB vaccine candidates and the only licensed TB vaccine, Bacillus Calmette-Guérin (BCG). We propose that the antigen-specific immune response induced by such vaccines provides an objective, data-driven basis for prioritisation of vaccine candidates for efficacy testing. We analyzed frequencies of antigen-specific CD4 and CD8 T cells expressing IFNγ, IL-2, TNF and/or IL-17 from adolescents or adults, with or without Mycobacterium tuberculosis (M.tb) infection, who received MVA85A, AERAS-402, H1:IC31, H56:IC31, M72/AS01E, ID93+GLA-SE or BCG. Two key response characteristics were analyzed, namely response magnitude and cytokine co-expression profile of the memory T cell response that persisted above the pre-vaccination response to the final study visit in each trial. All vaccines preferentially induced antigen-specif...Continue Reading

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Citations

Aug 15, 2019·Microorganisms·Erica StewartNikolai Petrovsky
Sep 4, 2019·The Journal of Clinical Investigation·Shabaana A KhaderUNKNOWN Bill and Melinda Gates Foundation Collaboration for TB Vaccine Discovery Innate Immunity Working Group18
Mar 20, 2020·Seminars in Immunopathology·Benedict Brazier, Helen McShane
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Sep 6, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claus AagaardRasmus Mortensen
Oct 9, 2020·Vaccines·E WhitlowS N M Hanif
Nov 20, 2020·Journal of Internal Medicine·R KuanC S Lindestam Arlehamn

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Methods Mentioned

BETA
PCA
flow cytometry

Clinical Trials Mentioned

NCT01865487
NCT00950612
NCT00460590
NCT00480558
NCT01927159
NCT01119521

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