B. anthracis has long been considered a potential biological warfare agent. One of the biodefense research priorities is to develop improved anthrax vaccines. Cell-mediated immune responses may play an important role in vaccine-induced protection against anthrax. Vgamma2Vdelta2 T cells exist only in primates and constitute 60-95% of total human gammadeltaT cell population in the blood. We have recently demonstrated that phosphoantigen-specific Vgamma2Vdelta2 T cells can contribute to adaptive immunity to fatal mycobacterial infection. We have also shown that B. anthracis, like mycobacteria, carries a novel gene encoding GcpE protein that mediates production of phosphoantigen recognized by Vgamma2Vdelta2 T cells. B. anthracis infection of monkeys could prime phosphoantigen-specific Vgamma2Vdelta2 T cells, and result in cross-reactive memory-type responses of these gammadeltaT cells after subsequent infection with phosphoantigen-producing mycobacteria. Since the current anthrax vaccine contains only protein antigens of B. anthracis, phosphoantigen may provide an important addition to anthrax vaccine regimens. We hypothesize that Vgamma2Vdelta2 T cells contribute to both innate and adaptive immune protection against B. anthracis infection. Since peptide-specific CD4 and CD8 T cells may play a role in immunity to anthrax, we further hypothesize that a combined vaccine targeting both phosphoantigen-specific Vgamma2Vdelta2 T cells and peptide-specific CD4 and CD8 T cells are more efficient for immunization and vaccine-induced protection against anthrax. In this R21 application, we will I. Determine vaccine-elicited immune responses of Vgamma2Vdelta2 T cells, and CD4 and CD8 T cells in macaques immunized with a combined vaccine comprised of phosphoantigen and protective antigen (PA) of B. anthracis. II. Determine if combined phosphoantigen and PA immunization of Vgamma2Vdelta2 T cells, CD4 and CD8 T cells can confer protective immunity to inhalation anthrax.
