Evaluation of granulysin and perforin as candidate biomarkers for protection following vaccination with Mycobacterium bovis BCG or M. bovis delta-RD1 (81.10)

Abstract

Abstract Development of improved vaccines against tuberculosis (TB) is directly correlated to the investigation of new and better correlates of protection after vaccination. We examined the kinetics of granulysin, perforin, IFN-gamma and Fas-L responses to M. bovis purified protein derivative (PPD) stimulation by peripheral blood mononuclear cells from BCG- and non-vaccinated cattle. Gene expression profiles following PPD stimulation showed significant increases in transcripts for granulysin and IFN-gamma in both CD4+ and CD8+ T cells in BCG-vaccinated as compared to non-vaccinated animals. Perforin & IFN-gamma examined by flow cytometry, showed a difference of 1-2% more PPD-specific cells in BCG-vaccinated than non-vaccinated animals. In a second trial, M. bovis BCG vaccinated animals had lower disease and pathological scores as compared to M. bovis Delta-RD1(a new vaccinate candidate) and the control group. Gene expression of granulysin and perforin were significantly increased in both vaccine groups (M. bovis BCG and M. bovis Delta-RD1 vaccinated) as compared to control after vaccination and challenge. IFN-gamma expression was increased only after vaccination and secretion was higher in the control, as compared to both vaccine groups demonstrating no correlation with protection upon vaccination.