A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication
PB10 IgG(1), a monoclonal antibody (MAb) directed against an immunodominant epitope on the enzymatic subunit (RTA) of ricin toxin (RT), has been shown to passively protect mice and non-human primates from an aerosolized lethal-dose RT challenge. However, it was recently demonstrated that the therape...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232472/ https://www.ncbi.nlm.nih.gov/pubmed/32235318 http://dx.doi.org/10.3390/toxins12040215 |
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author | Rong, Yinghui Pauly, Michael Guthals, Adrian Pham, Henry Ehrbar, Dylan Zeitlin, Larry Mantis, Nicholas J. |
author_facet | Rong, Yinghui Pauly, Michael Guthals, Adrian Pham, Henry Ehrbar, Dylan Zeitlin, Larry Mantis, Nicholas J. |
author_sort | Rong, Yinghui |
collection | PubMed |
description | PB10 IgG(1), a monoclonal antibody (MAb) directed against an immunodominant epitope on the enzymatic subunit (RTA) of ricin toxin (RT), has been shown to passively protect mice and non-human primates from an aerosolized lethal-dose RT challenge. However, it was recently demonstrated that the therapeutic efficacy of PB10 IgG1 is significantly improved when co-administered with a second MAb, SylH3, targeting RT’s binding subunit (RTB). Here we report that the PB10/SylH3 cocktail is also superior to PB10 alone when used as a pre-exposure prophylactic (PrEP) in a mouse model of intranasal RT challenge. The benefit of the PB10/SylH3 cocktail prompted us to engineer a humanized IgG1 version of SylH3 (huSylH3). The huPB10/huSylH3 cocktail proved highly efficacious in the mouse model, thereby opening the door to future testing in non-human primates. |
format | Online Article Text |
id | pubmed-7232472 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72324722020-05-22 A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication Rong, Yinghui Pauly, Michael Guthals, Adrian Pham, Henry Ehrbar, Dylan Zeitlin, Larry Mantis, Nicholas J. Toxins (Basel) Article PB10 IgG(1), a monoclonal antibody (MAb) directed against an immunodominant epitope on the enzymatic subunit (RTA) of ricin toxin (RT), has been shown to passively protect mice and non-human primates from an aerosolized lethal-dose RT challenge. However, it was recently demonstrated that the therapeutic efficacy of PB10 IgG1 is significantly improved when co-administered with a second MAb, SylH3, targeting RT’s binding subunit (RTB). Here we report that the PB10/SylH3 cocktail is also superior to PB10 alone when used as a pre-exposure prophylactic (PrEP) in a mouse model of intranasal RT challenge. The benefit of the PB10/SylH3 cocktail prompted us to engineer a humanized IgG1 version of SylH3 (huSylH3). The huPB10/huSylH3 cocktail proved highly efficacious in the mouse model, thereby opening the door to future testing in non-human primates. MDPI 2020-03-29 /pmc/articles/PMC7232472/ /pubmed/32235318 http://dx.doi.org/10.3390/toxins12040215 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rong, Yinghui Pauly, Michael Guthals, Adrian Pham, Henry Ehrbar, Dylan Zeitlin, Larry Mantis, Nicholas J. A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication |
title | A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication |
title_full | A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication |
title_fullStr | A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication |
title_full_unstemmed | A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication |
title_short | A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication |
title_sort | humanized monoclonal antibody cocktail to prevent pulmonary ricin intoxication |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232472/ https://www.ncbi.nlm.nih.gov/pubmed/32235318 http://dx.doi.org/10.3390/toxins12040215 |
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