The recombinant tuberculosis vaccine rBCG ΔureC::hly+ induces apoptotic vesicles for improved priming of CD4+ and CD8+ T cells

Background: The recombinant BCG Delta ureC::hly(+) (rBCG) vaccine candidate is more efficient than parental BCG (pBCG) against tuberculosis (TB) in preclinical models. Evidence exists for superior CD4 and CD8 T cell stimulation. Although the responsible immune mechanisms are incompletely understood, crosspriming of CD8 T cells has been proposed as a major mechanism underlying better protection of rBCG over pBCG. The present study investigates the role of apoptotic vesicles from pBCG- and rBCG-infected macrophages in crosspriming. Methods: Apoptotic vesicles were isolated from pBCG- and rBCG-infected mouse macrophages. The priming potential of the isolated vesicles was evaluated in terms of dendritic cell activation and specific T cell stimulation. Results: Apoptotic vesicles from both pBCG- and rBCG-infected macrophages activated dendritic cells but to a different degree. Overall, rBCG-infected apoptotic vesicles induced more profound CD4 and CD8 T cell responses as compared to pBCG. Conclusions: These data support the notion that the improved vaccine efficacy of rBCG rests on enhanced crosspriming as a consequence of stronger apoptosis. (C) 2012 Elsevier Ltd. All rights reserved.