Efficacy of Urtoxazumab (TMA-15 Humanized Monoclonal Antibody Specific for Shiga Toxin 2) Against Post-Diarrheal Neurological Sequelae Caused by Escherichia coli O157:H7 Infection in the Neonatal Gnotobiotic Piglet Model
Enterohemorrhagic Escherichia coli (EHEC) is the most common cause of hemorrhagic colitis and hemolytic uremic syndrome in human patients, with brain damage and dysfunction the main cause of acute death. We evaluated the efficacy of urtoxazumab (TMA-15, Teijin Pharma Limited), a humanized monoclonal...
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| Format: | Article |
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MDPI AG
2017-01-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/9/2/49 |
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| author | Rodney A. Moxley David H. Francis Mizuho Tamura David B. Marx Kristina Santiago-Mateo Mojun Zhao |
| author_facet | Rodney A. Moxley David H. Francis Mizuho Tamura David B. Marx Kristina Santiago-Mateo Mojun Zhao |
| author_sort | Rodney A. Moxley |
| collection | DOAJ |
| description | Enterohemorrhagic Escherichia coli (EHEC) is the most common cause of hemorrhagic colitis and hemolytic uremic syndrome in human patients, with brain damage and dysfunction the main cause of acute death. We evaluated the efficacy of urtoxazumab (TMA-15, Teijin Pharma Limited), a humanized monoclonal antibody against Shiga toxin (Stx) 2 for the prevention of brain damage, dysfunction, and death in a piglet EHEC infection model. Forty-five neonatal gnotobiotic piglets were inoculated orally with 3 × 109 colony-forming units of EHEC O157:H7 strain EDL933 (Stx1+, Stx2+) when 22–24 h old. At 24 h post-inoculation, piglets were intraperitoneally administered placebo or TMA-15 (0.3, 1.0 or 3.0 mg/kg body weight). Compared to placebo (n = 10), TMA-15 (n = 35) yielded a significantly greater probability of survival, length of survival, and weight gain (p <0.05). The efficacy of TMA-15 against brain lesions and death was 62.9% (p = 0.0004) and 71.4% (p = 0.0004), respectively. These results suggest that TMA-15 may potentially prevent or reduce vascular necrosis and infarction of the brain attributable to Stx2 in human patients acutely infected with EHEC. However, we do not infer that TMA-15 treatment will completely protect human patients infected with EHEC O157:H7 strains that produce both Stx1 and Stx2. |
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| id | doaj.art-55b5d9e815854c30a2662682194e303e |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-12T19:42:13Z |
| publishDate | 2017-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-55b5d9e815854c30a2662682194e303e2022-12-22T03:19:03ZengMDPI AGToxins2072-66512017-01-01924910.3390/toxins9020049toxins9020049Efficacy of Urtoxazumab (TMA-15 Humanized Monoclonal Antibody Specific for Shiga Toxin 2) Against Post-Diarrheal Neurological Sequelae Caused by Escherichia coli O157:H7 Infection in the Neonatal Gnotobiotic Piglet ModelRodney A. Moxley0David H. Francis1Mizuho Tamura2David B. Marx3Kristina Santiago-Mateo4Mojun Zhao5School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USATeijin Pharma Limited, Pharmacology Research Department, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, JapanDepartment of Statistics, University of Nebraska-Lincoln, Lincoln, NE 68583, USACanadian Food Inspection Agency, Lethbridge Laboratory, Box 640 TWP Rd 9-1, Lethbridge, AB T1J 3Z4, CanadaValley Pathologists, Inc., 1100 South Main Street, Suite 308, Dayton, OH 45409, USAEnterohemorrhagic Escherichia coli (EHEC) is the most common cause of hemorrhagic colitis and hemolytic uremic syndrome in human patients, with brain damage and dysfunction the main cause of acute death. We evaluated the efficacy of urtoxazumab (TMA-15, Teijin Pharma Limited), a humanized monoclonal antibody against Shiga toxin (Stx) 2 for the prevention of brain damage, dysfunction, and death in a piglet EHEC infection model. Forty-five neonatal gnotobiotic piglets were inoculated orally with 3 × 109 colony-forming units of EHEC O157:H7 strain EDL933 (Stx1+, Stx2+) when 22–24 h old. At 24 h post-inoculation, piglets were intraperitoneally administered placebo or TMA-15 (0.3, 1.0 or 3.0 mg/kg body weight). Compared to placebo (n = 10), TMA-15 (n = 35) yielded a significantly greater probability of survival, length of survival, and weight gain (p <0.05). The efficacy of TMA-15 against brain lesions and death was 62.9% (p = 0.0004) and 71.4% (p = 0.0004), respectively. These results suggest that TMA-15 may potentially prevent or reduce vascular necrosis and infarction of the brain attributable to Stx2 in human patients acutely infected with EHEC. However, we do not infer that TMA-15 treatment will completely protect human patients infected with EHEC O157:H7 strains that produce both Stx1 and Stx2.http://www.mdpi.com/2072-6651/9/2/49Shiga toxinenterohemorrhagic E. colignotobiotic pigletsmonoclonal antibody |
| spellingShingle | Rodney A. Moxley David H. Francis Mizuho Tamura David B. Marx Kristina Santiago-Mateo Mojun Zhao Efficacy of Urtoxazumab (TMA-15 Humanized Monoclonal Antibody Specific for Shiga Toxin 2) Against Post-Diarrheal Neurological Sequelae Caused by Escherichia coli O157:H7 Infection in the Neonatal Gnotobiotic Piglet Model Toxins Shiga toxin enterohemorrhagic E. coli gnotobiotic piglets monoclonal antibody |
| title | Efficacy of Urtoxazumab (TMA-15 Humanized Monoclonal Antibody Specific for Shiga Toxin 2) Against Post-Diarrheal Neurological Sequelae Caused by Escherichia coli O157:H7 Infection in the Neonatal Gnotobiotic Piglet Model |
| title_full | Efficacy of Urtoxazumab (TMA-15 Humanized Monoclonal Antibody Specific for Shiga Toxin 2) Against Post-Diarrheal Neurological Sequelae Caused by Escherichia coli O157:H7 Infection in the Neonatal Gnotobiotic Piglet Model |
| title_fullStr | Efficacy of Urtoxazumab (TMA-15 Humanized Monoclonal Antibody Specific for Shiga Toxin 2) Against Post-Diarrheal Neurological Sequelae Caused by Escherichia coli O157:H7 Infection in the Neonatal Gnotobiotic Piglet Model |
| title_full_unstemmed | Efficacy of Urtoxazumab (TMA-15 Humanized Monoclonal Antibody Specific for Shiga Toxin 2) Against Post-Diarrheal Neurological Sequelae Caused by Escherichia coli O157:H7 Infection in the Neonatal Gnotobiotic Piglet Model |
| title_short | Efficacy of Urtoxazumab (TMA-15 Humanized Monoclonal Antibody Specific for Shiga Toxin 2) Against Post-Diarrheal Neurological Sequelae Caused by Escherichia coli O157:H7 Infection in the Neonatal Gnotobiotic Piglet Model |
| title_sort | efficacy of urtoxazumab tma 15 humanized monoclonal antibody specific for shiga toxin 2 against post diarrheal neurological sequelae caused by escherichia coli o157 h7 infection in the neonatal gnotobiotic piglet model |
| topic | Shiga toxin enterohemorrhagic E. coli gnotobiotic piglets monoclonal antibody |
| url | http://www.mdpi.com/2072-6651/9/2/49 |
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