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

Vaccine. 2022 Jul 30;40(32):4318-4321. doi: 10.1016/j.vaccine.2022.06.023. Epub 2022 Jun 14.

Abstract

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.

Keywords: Anthrax protective antigen; CMG2 receptor; CMG2-null mice; Toxin-neutralizing antibodies.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Anthrax*
  • Antibodies, Neutralizing
  • Antigens, Bacterial
  • Bacterial Toxins
  • Mammals / metabolism
  • Mice
  • Morphogenesis
  • Receptors, Peptide* / genetics
  • Receptors, Peptide* / metabolism

Substances

  • Antibodies, Neutralizing
  • Antigens, Bacterial
  • Bacterial Toxins
  • Receptors, Peptide
  • anthrax toxin