T cell immunity to B. anthracis

描述（由申请人提供）：B。炭疽病一直被认为是一种潜在的生物战剂。生物防御研究的优先事项之一是开发改进的炭疽疫苗。细胞介导的免疫应答可能在疫苗诱导的抗炭疽保护中起重要作用。V γ 2 V δ 2 T细胞仅存在于灵长类动物中，占血液中总人γ δ T细胞群的60-95%。我们最近已经证明，磷酸化抗原特异性V γ 2 V δ 2 T细胞可以促进对致命性分枝杆菌感染的适应性免疫。我们还证明了B.炭疽杆菌和分枝杆菌一样，携带一种编码GcpE蛋白的新基因，该基因介导由V γ 2 V δ 2 T细胞识别的磷酸化抗原的产生。B。炭疽感染猴子可以引发磷酸化抗原特异性V γ 2 V δ 2 T细胞，并在随后感染产生磷酸化抗原的分枝杆菌后导致这些γ δ T细胞的交叉反应性记忆型应答。由于目前的炭疽疫苗只含有B的蛋白抗原。在炭疽病中，磷酸化抗原可能为炭疽疫苗方案提供重要补充。我们假设V γ 2 V δ 2 T细胞有助于针对B的先天性和适应性免疫保护。炭疽感染。由于肽特异性CD 4和CD 8 T细胞可能在炭疽免疫中发挥作用，我们进一步假设，靶向磷酸化抗原特异性V γ 2 V δ 2 T细胞和肽特异性CD 4和CD 8 T细胞的联合疫苗对于免疫和疫苗诱导的炭疽保护更有效。在这个R21应用程序中，我们将 I.测定用由B的磷抗原和保护性抗原（PA）组成的组合疫苗免疫的猕猴中V γ 2 V δ 2 T细胞以及CD 4和CD 8 T细胞的疫苗引发的免疫应答。炭疽病 二.确定V γ 2 V δ 2 T细胞、CD 4和CD 8 T细胞的组合磷酸化抗原和PA免疫是否可以赋予对吸入性炭疽的保护性免疫。

DESCRIPTION (provided by applicant): 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.