Inability of the BCG vaccine to protect mice of the H2f haplotype at advanced stages of TB infection is associated with defective CD4+ T-cell activation in spleen.

We performed studies in B10.M H2-congenic mouse strain whose H2f haplotype is associated with defective BCG vaccination efficacy against TB challenge. No difference in mortality dynamics between BCG-vaccinated and primarily infected B10.M mice was observed, whereas in B10 (H2b) congenic mice BCG vaccination significantly prolonged survival. At the early stages of infection, vaccinated mice of both strains controlled mycobacterial multiplication in lungs and draining lymph nodes better than non-vaccinated, however, in B10.M spleens no vaccination effect was evident. More activated cells expressing the CD4+CD44+CD62L- phenotype resided in spleens of vaccinated B10 compared to B10.M mice. Our results suggest that inability of BCG vaccination to prolong survival of TB-infected B10.M mice may be associated with defective response to disseminated rather than primary infection.