A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication
PB10 IgG<sub>1</sub>, 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 demonstr...
| Published in: | Toxins |
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| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-03-01
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| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6651/12/4/215 |
| _version_ | 1850097089780908032 |
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| author | Yinghui Rong Michael Pauly Adrian Guthals Henry Pham Dylan Ehrbar Larry Zeitlin Nicholas J. Mantis |
| author_facet | Yinghui Rong Michael Pauly Adrian Guthals Henry Pham Dylan Ehrbar Larry Zeitlin Nicholas J. Mantis |
| author_sort | Yinghui Rong |
| collection | DOAJ |
| container_title | Toxins |
| description | PB10 IgG<sub>1</sub>, 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 | Article |
| id | doaj-art-fa52682f77ed4722b6040fc129dc91c5 |
| institution | Directory of Open Access Journals |
| issn | 2072-6651 |
| language | English |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| spelling | doaj-art-fa52682f77ed4722b6040fc129dc91c52025-08-20T00:06:25ZengMDPI AGToxins2072-66512020-03-0112421510.3390/toxins12040215A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin IntoxicationYinghui Rong0Michael Pauly1Adrian Guthals2Henry Pham3Dylan Ehrbar4Larry Zeitlin5Nicholas J. Mantis6Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY 12208, USAMapp Biopharmaceutical, Inc. 6160 Lusk Blvd, San Diego, CA 92121, USAMapp Biopharmaceutical, Inc. 6160 Lusk Blvd, San Diego, CA 92121, USAMapp Biopharmaceutical, Inc. 6160 Lusk Blvd, San Diego, CA 92121, USADivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY 12208, USAMapp Biopharmaceutical, Inc. 6160 Lusk Blvd, San Diego, CA 92121, USADivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY 12208, USAPB10 IgG<sub>1</sub>, 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.https://www.mdpi.com/2072-6651/12/4/215toxinlungantibodybiodefenseprophylactic |
| spellingShingle | Yinghui Rong Michael Pauly Adrian Guthals Henry Pham Dylan Ehrbar Larry Zeitlin Nicholas J. Mantis A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication toxin lung antibody biodefense prophylactic |
| 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 | toxin lung antibody biodefense prophylactic |
| url | https://www.mdpi.com/2072-6651/12/4/215 |
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