A monoclonal antibody to Bacillus anthracis protective antigen defines a neutralizing epitope in domain 1

Johanna Rivera, Antonio Nakouzi, Nareen Abboud, Ekaterina Revskaya, David L. Goldman, R. John Collier, Ekaterina Dadachova, Arturo Casadevall

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Antibody (Ab) responses to Bacillus anthracis toxins are protective, but relatively few protective monoclonal antibodies (MAbs) have been reported. Protective antigen (PA) is essential for the action of B. anthracis lethal toxin (LeTx) and edema toxin. In this study, we generated two MAbs to PA, MAbs 7.5G and 10F4. These MAbs did not compete for binding to PA, consistent with specificities for different epitopes. The MAbs were tested for their ability to protect a monolayer of cultured macrophages against toxin-mediated cytotoxicity. MAb 7.5G, the most-neutralizing MAb, bound to domain 1 of PA and reduced LeTx toxicity in BALB/c mice. Remarkably, MAb 7.5G provided protection without blocking the binding of PA or lethal factor or the formation of the PA heptamer complex. However, MAb 7.5G slowed the proteolytic digestion of PA by furin in vitro, suggesting a potential mechanism for Ab-mediated protection. These observations indicate that some Abs to domain 1 can contribute to host protection.

Original languageEnglish (US)
Pages (from-to)4149-4156
Number of pages8
JournalInfection and Immunity
Volume74
Issue number7
DOIs
StatePublished - Jul 2006

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Epitopes
Monoclonal Antibodies
Antigens
Furin
Bacillus anthracis
anthrax toxin
Antibody Formation
Digestion
Edema
Macrophages
Antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

A monoclonal antibody to Bacillus anthracis protective antigen defines a neutralizing epitope in domain 1. / Rivera, Johanna; Nakouzi, Antonio; Abboud, Nareen; Revskaya, Ekaterina; Goldman, David L.; Collier, R. John; Dadachova, Ekaterina; Casadevall, Arturo.

In: Infection and Immunity, Vol. 74, No. 7, 07.2006, p. 4149-4156.

Research output: Contribution to journalArticle

Rivera, Johanna ; Nakouzi, Antonio ; Abboud, Nareen ; Revskaya, Ekaterina ; Goldman, David L. ; Collier, R. John ; Dadachova, Ekaterina ; Casadevall, Arturo. / A monoclonal antibody to Bacillus anthracis protective antigen defines a neutralizing epitope in domain 1. In: Infection and Immunity. 2006 ; Vol. 74, No. 7. pp. 4149-4156.
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