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BCG vaccination-induced acquired control of mycobacterial growth differs from growth control preexisting to BCG vaccination

  • Krista E. van Meijgaarden,
  • Wenchao Li,
  • Simone J. C. F. M. Moorlag,
  • Valerie A. C. M. Koeken,
  • Hans J. P. M. Koenen,
  • Leo A. B. Joosten,
  • Annapurna Vyakarnam,
  • Asma Ahmed,
  • Srabanti Rakshit,
  • Vasista Adiga,
  • Tom H. M. Ottenhoff,
  • Yang Li,
  • Mihai G. Netea,
  • Simone A. Joosten

摘要

Bacillus Calmette-Guèrin - vaccination induces not only protection in infants and young children against severe forms of tuberculosis, but also against non-tuberculosis related all-cause mortality. To delineate different factors influencing mycobacterial growth control, here we first investigate the effects of BCG-vaccination in healthy Dutch adults. About a quarter of individuals already control BCG-growth prior to vaccination, whereas a quarter of the vaccinees acquires the capacity to control BCG upon vaccination. This leaves half of the population incapable to control BCG-growth. Single cell RNA sequencing identifies multiple processes associated with mycobacterial growth control. These data suggest (i) that already controllers employ different mechanisms to control BCG-growth than acquired controllers, and (ii) that half of the individuals fail to develop measurable growth control irrespective of BCG-vaccination. These results shed important new light on the variable immune responses to mycobacteria in humans and may impact on improved vaccination against tuberculosis and other diseases.