Preexisting Inflammation Due toMycobacterium bovisBCG Infection Differentially Modulates T-Cell Priming against a Replicating or Nonreplicating Immunogen

Induction of T-cell memory by vaccination ensures long-term protection against pathogens. We determined whether on-going inflammatory responses during vaccination influenced T-cell priming. A preexposure of mice toMycobacterium bovisBCG impaired their subsequent ability to prime T cells againstListeria monocytogenes. This was characterized by a decrease inL. monocytogenes-specific gamma interferon (IFN-γ)-secreting CD4+and CD8+T cells. The intensity of T-cell priming towardsL. monocytogenesdepended on the extent ofL. monocytogenesexpansion, and a cessation of this expansion caused byM. bovisBCG-induced inflammation resulted in impairment in T-cell priming. A challenge ofM. bovisBCG-infected mice with a higherL. monocytogenesdose increasedL. monocytogenessurvival and restored T-cell priming towardsL. monocytogenes. Impairment in T-cell priming towardsL. monocytogenesdue toM. bovisBCG-induced inflammation resulted in a compromised protective efficacy in the long term after mice were rechallenged withL. monocytogenes. Preexisting inflammation selectively impaired T-cell priming for replicating immunogens as CD8+T-cell response to ovalbumin administered as an inert antigen (ovalbumin-archaeosomes) was enhanced byM. bovisBCG preimmunization, whereas priming towards ovalbumin administered as a live immunogen (L. monocytogenes-ovalbumin) was impaired. Thus, depending on the nature of the immunogen, the presence of prior inflammatory responses may either impede or boost vaccine efficacy.