The CD8+ T cell response to Brucella melitensis during acute vs. chronic infection (40.24)

Abstract In areas of endemic brucellosis, prevention of infection via vaccine would be far more cost-effective than the World Health Organization suggested regimen of antibiotics. As with other intracellular organisms, subunit or killed vaccines present very limited efficacy. The rationale for an improved Brucella melitensis vaccine requires a greater understanding of the host-pathogen relationship. Using bioinformatics coupled with practical experiments in the BALB/c model of brucellosis, we have identified two Brucella epitopes and show their capacity to elicit specific CD8+ T cells that kill effectively in vivo. Additionally, as seen by microarray, gene transcripts that contain these epitopes are significantly and differentially expressed following Brucella infection of macrophages. Specific CD8+ T cells are present and functional following infection; however, reactivation of disease still occurs in up to 30% of human patients after antibiotic treatment. Our current work using Brucella specific MHC Class I tetramers focuses on the presence and persistence of CD8+ T cell memory during chronic brucellosis. Investigation of the functional potential of this memory fraction of CD8+ T cells will fill a gap in our understanding of the immunological response to this often asymptomatic, persistent infection.