A monoclonal antibody to Bacillus anthracis protective antigen defines a neutralizing epitope in domain 1
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.
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2006 |
|---|---|
| Erschienen: |
2006 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:74 |
|---|---|
| Enthalten in: |
Infection and immunity - 74(2006), 7 vom: 19. Juli, Seite 4149-56 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Rivera, Johanna [VerfasserIn] |
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| Themen: |
Anthrax toxin |
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| Anmerkungen: |
Date Completed 24.08.2006 Date Revised 12.04.2024 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM163660409 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
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| 003 | DE-627 | ||
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| 041 | |a eng | ||
| 100 | 1 | |a Rivera, Johanna |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A monoclonal antibody to Bacillus anthracis protective antigen defines a neutralizing epitope in domain 1 |
| 264 | 1 | |c 2006 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 24.08.2006 | ||
| 500 | |a Date Revised 12.04.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antigens, Bacterial |2 NLM | |
| 650 | 7 | |a Bacterial Toxins |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a anthrax toxin |2 NLM | |
| 700 | 1 | |a Nakouzi, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Abboud, Nareen |e verfasserin |4 aut | |
| 700 | 1 | |a Revskaya, Ekaterina |e verfasserin |4 aut | |
| 700 | 1 | |a Goldman, David |e verfasserin |4 aut | |
| 700 | 1 | |a Collier, R John |e verfasserin |4 aut | |
| 700 | 1 | |a Dadachova, Ekaterina |e verfasserin |4 aut | |
| 700 | 1 | |a Casadevall, Arturo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Infection and immunity |d 1970 |g 74(2006), 7 vom: 19. Juli, Seite 4149-56 |w (DE-627)NLM000004278 |x 1098-5522 |7 nnns |
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