T-cell activation is an immune correlate of risk in BCG vaccinated infants

نویسندگان

  • Helen A Fletcher
  • Margaret A Snowden
  • Bernard Landry
  • Wasima Rida
  • Iman Satti
  • Stephanie A Harris
  • Magali Matsumiya
  • Rachel Tanner
  • Matthew K O'Shea
  • Veerabadran Dheenadhayalan
  • Leah Bogardus
  • Lisa Stockdale
  • Leanne Marsay
  • Agnieszka Chomka
  • Rachel Harrington-Kandt
  • Zita-Rose Manjaly-Thomas
  • Vivek Naranbhai
  • Elena Stylianou
  • Fatoumatta Darboe
  • Adam Penn-Nicholson
  • Elisa Nemes
  • Mark Hatheril
  • Gregory Hussey
  • Hassan Mahomed
  • Michele Tameris
  • J Bruce McClain
  • Thomas G Evans
  • Willem A Hanekom
  • Thomas J Scriba
  • Helen McShane
چکیده

Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case-control analysis to identify immune correlates of TB disease risk in Bacille Calmette-Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR(+) CD4(+) T cells associates with increased TB disease risk (OR=1.828, 95% CI=1.25-2.68, P=0.002, FDR=0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR(+) CD4(+) T cells also associate with increased TB disease risk (OR=1.387, 95% CI=1.068-1.801, P=0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN-γ associate with reduced risk of TB (OR=0.502, 95% CI=0.29-0.86, P=0.013, FDR=0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations.

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عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2016