Abstract: Immunogenic compositions against Bacillus anthracis comprising a stabilized protective antigen complex are disclosed. The stabilized complex comprises protective antigen protein and capillary morphogenesis protein-2, with the capillary morphogenesis protein-2 being bound to the protective antigen protein along a binding interface. The stabilized protective antigen complex has increased thermal and structural stability, along with resistance to premature proteolytic degradation. Methods of using the same to induce an immunogenic response in a subject against B. anthracis infection are also disclosed.

Abstract: Immunogenic compositions against Bacillus anthracis comprising a stabilized protective antigen complex are disclosed. The stabilized complex comprises protective antigen protein and capillary morphogenesis protein-2, with the capillary morphogenesis protein-2 being bound to the protective antigen protein along a binding interface. The stabilized protective antigen complex has increased thermal and structural stability, along with resistance to premature proteolytic degradation. Methods of using the same to induce an immunogenic response in a subject against B. anthracis infection are also disclosed.

Abstract: Immunogenic compositions against Bacillus anthracis comprising a stabilized protective antigen complex are disclosed. The stabilized complex comprises protective antigen protein and capillary morphogenesis protein-2, with the capillary morphogenesis protein-2 being bound to the protective antigen protein along a binding interface. The stabilized protective antigen complex has increased thermal and structural stability, along with resistance to premature proteolytic degradation. Methods of using the same to induce an immunogenic response in a subject against B. anthracis infection are also disclosed.

Abstract: The unnatural amino acid analogue 2-fluorohistidine (2-FHis) was incorporated into protective antigen to produce a protein which resists protonation at physiological pH by reducing the side-chain pKa. The protein structure was unperturbed by the incorporation of fluorinated histidine residues, and the heptameric (2-FHisPA63)7 could form ion conducting channels, and bind to the PA-binding domain of LF (LFN), but translocation of LFN in planar lipid bilayers was blocked. Further, while (2-FHisPA63)7 could bind to host cells and in vitro to the host cellular receptor, pore formation in the presence of the receptor was blocked, and LFN-DTA mediated cytotoxicity in CHO-K1 cells was blocked. The modified PA is useful as both a vaccine and an antitoxin, providing epitopes for the production of antibodies against PA, but preventing key steps in pathogenesis (pore formation, translocation).

Abstract: The unnatural amino acid analogue 2-fluorohistidine (2-FHis) was incorporated into protective antigen to produce a protein which resists protonation at physiological pH by reducing the side-chain pKa. The protein structure was unperturbed by the incorporation of fluorinated histidine residues, and the heptameric (2-FHisPA63)7 could form ion conducting channels, and bind to the PA-binding domain of LF (LFN), but translocation of LFN in planar lipid bilayers was blocked. Further, while (2-FHisPA63)7 could bind to host cells and in vitro to the host cellular receptor, pore formation in the presence of the receptor was blocked, and LFN-DTA mediated cytotoxicity in CHO-K1 cells was blocked. The modified PA is useful as both a vaccine and an antitoxin, providing epitopes for the production of antibodies against PA, but preventing key steps in pathogenesis (pore formation, translocation).