Skip to Main content Skip to Navigation
Journal articles

Functional Analysis of Bacillus anthracis Protective Antigen by Using Neutralizing Monoclonal Antibodies

Abstract : Protective antigen (PA) is central to the action of the lethal and edema toxins produced by Bacillus anthracis . It is the common cell-binding component, mediating the translocation of the enzymatic moieties (lethal factor [LF] and edema factor) into the cytoplasm of the host cell. Monoclonal antibodies (MAbs) against PA, able to neutralize the activities of the toxins in vitro and in vivo, were screened. Two such MAbs, named 7.5 and 48.3, were purified and further characterized. MAb 7.5 binds to domain 4 of PA and prevents the binding of PA to its cell receptor. MAb 48.3 binds to domain 2 and blocks the cleavage of PA into PA63, a step necessary for the subsequent interaction with the enzymatic moieties. The epitope recognized by this antibody is in a region involved in the oligomerization of PA63; thus, MAb 48.3 does not recognize the oligomer form. MAbs 7.5 and 48.3 neutralize the activities of anthrax toxins produced by B. anthracis in mice. Also, there is an additive effect between the two MAbs against PA and a MAb against LF, in protecting mice against a lethal challenge by the Sterne strain. This work contributes to the functional analysis of PA and offers immunotherapeutic perspectives for the treatment of anthrax disease.
Document type :
Journal articles
Complete list of metadata

https://hal-pasteur.archives-ouvertes.fr/pasteur-03507697
Contributor : Pierre Lafaye Connect in order to contact the contributor
Submitted on : Monday, January 3, 2022 - 12:41:14 PM
Last modification on : Wednesday, January 5, 2022 - 1:10:01 PM

Links full text

Identifiers

Collections

Citation

Fabien Brossier, Martine Lévy, Annie Landier, Pierre Lafaye, Michèle Mock, et al.. Functional Analysis of Bacillus anthracis Protective Antigen by Using Neutralizing Monoclonal Antibodies. Infection and Immunity, American Society for Microbiology, 2004, 72 (11), pp.6313-6317. ⟨10.1128/IAI.72.11.6313-6317.2004⟩. ⟨pasteur-03507697⟩

Share

Metrics

Les métriques sont temporairement indisponibles