Receptor-enhanced immunogenicity of anthrax protective antigen is primarily mediated by capillary morphogenesis Protein-2

Anthrax protective antigen (PA), the receptor-binding component of anthrax toxin, elicits toxin-neutralizing antibodies which provide protection against anthrax disease. PA binds to two mammalian receptors, capillary morphogenesis protein-2 (CMG2) and tumor endothelial marker-8 (TEM8). We previously observed that binding of PA to its receptors plays a role in eliciting a strong toxin-neutralizing antibody response. In this study, we examined the roles that individual receptors play in mediating the toxin-neutralizing antibody response. Mice immunized with PA that binds preferentially to CMG2 elicited a toxin-neutralizing antibody response similar to that elicited by wild-type PA, whereas the antibody response elicited by PA that binds preferentially to TEM8 was significantly lower. Also, the toxin-neutralizing antibody response elicited by wild-type PA in CMG2-null mice was found to be significantly lower than that induced in CMG2-sufficient mice, further supporting a predominant role for the CMG2 receptor in mediating a protective antibody response to PA.