Persistent BCG bacilli perpetuate CD4 T effector memory and optimal protection against tuberculosis

• DOI: 10.1016/j.vaccine.2014.10.041
• Publication Date: 2014-11-04T06:56:56Z
• Authors: Daryan A. Kaveh; M.C. Garcia-Pelayo; Philip J. Hogarth
• Keywords: Priming (agriculture); BCG vaccine

Tuberculosis (TB) remains one of the most important infectious diseases man and animals, only available vaccine (BCG) requires urgent replacement or improvement. To facilitate this, protective mechanisms induced by BCG require further understanding. As a live attenuated vaccine, persistence bacilli in host may be crucial mechanism. We have investigated long term following vaccination influence on immune response protection, using an established murine model. sought to establish whether previously identified BCG-specific CD4 TEM cells represent genuine long-lived memory relatively high frequency, are consequence continual priming chronically persistent bacilli. By clearing bacilli, we compared responses (spleen lung CD4: cytokine producing T effector/TEM; TCR-specific) BCG-induced presence absence these persisting Viable persisted for at least 16 months post-vaccination, associated with specific effector/TEM tetramer-specific responses. Clearing abrogated all whilst reducing protection 1log10. induce two additive immunity: (i) dependant viable TEM; (ii) independent factors. These data implications rational generation TB vaccines, interpretation immunity animal models.