T-cell Activation Is an Immune Correlate of Risk in BCG Vaccinated Infants

Nat Commun. 2016 Apr 12;7:11290. doi: 10.1038/ncomms11290.

Abstract

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Antibody Formation / immunology
  • BCG Vaccine / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Case-Control Studies
  • Cohort Studies
  • HLA-DR Antigens / immunology
  • Humans
  • Immunity
  • Immunoglobulin G / immunology
  • Infant
  • Logistic Models
  • Lymphocyte Activation / immunology*
  • Mycobacterium tuberculosis / immunology
  • Placebos
  • Risk Factors
  • Time Factors
  • Tuberculosis / blood
  • Tuberculosis / immunology
  • Tuberculosis Vaccines / immunology
  • Vaccination*

Substances

  • BCG Vaccine
  • HLA-DR Antigens
  • Immunoglobulin G
  • MVA 85A
  • Placebos
  • Tuberculosis Vaccines