Purified Immunoglobulin F(ab′) 2 Protects Mice and Rhesus Monkeys against Lethal Ricin Intoxication
Ricin is a highly toxic ribosome-inactivating lectin derived from castor beans. To date, no antidote is available to treat ricin-poisoned patients, and the development of a safe and effective antidote is urgently needed. First, ricin was prepared and used to construct a mouse model and a rhesus monk...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Compuscript Ltd
2023-03-01
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| Series: | Zoonoses |
| Online Access: | https://www.scienceopen.com/hosted-document?doi=10.15212/ZOONOSES-2022-0050 |
| _version_ | 1797399408437886976 |
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| author | Jingjing Tian Cong Li Bochang Shi Hui Han Yuan Liu Lingyun Tan Keyu Wang Fang Yan Wei He Bo Li Naxin Zheng Huabin Li Xinyu Li Chongyu Tian Yuanqiang Zheng Zhongpeng Zhao Ruiwen Fan |
| author_facet | Jingjing Tian Cong Li Bochang Shi Hui Han Yuan Liu Lingyun Tan Keyu Wang Fang Yan Wei He Bo Li Naxin Zheng Huabin Li Xinyu Li Chongyu Tian Yuanqiang Zheng Zhongpeng Zhao Ruiwen Fan |
| author_sort | Jingjing Tian |
| collection | DOAJ |
| description | Ricin is a highly toxic ribosome-inactivating lectin derived from castor beans. To date, no antidote is available to treat ricin-poisoned patients, and the development of a safe and effective antidote is urgently needed. First, ricin was prepared and used to construct a mouse model and a rhesus monkey model of ricin intoxication. Second, pepsin-digested F(ab′) 2 fragments of serum IgG from horses injected with Freund’s-adjuvanted purified ricin were prepared. Third, the protective efficacy was evaluated in mouse and rhesus monkey models of lethal ricin intoxication. The purity quotient of the prepared ricin and F(ab′) 2 fragments exceeded 90% and 85% in the mouse and monkey models, respectively. The LD 50 of ricin in mice and rhesus monkeys was 2.7 and 9 μg/kg, respectively. A quantity of 6.25 and 1.85 mg/kg F(ab′) 2 was sufficient to treat lethal ricin intoxication in the mice and rhesus monkeys, respectively. Finally, the effect of this therapeutic antibody on peripheral blood immune cells was examined by analysis of peripheral blood immune cells through single cell sequencing. The underlying mechanism was found to involve restraining neutrophil activation, proliferation, and differentiation. Purified F(ab′) 2 fragments administered with needle-free devices fully protect mice and rhesus monkeys against lethal doses of ricin intoxication. |
| first_indexed | 2024-03-09T01:39:50Z |
| format | Article |
| id | doaj.art-25e2018f50834540866d7cd28ce1bb80 |
| institution | Directory Open Access Journal |
| issn | 2737-7466 2737-7474 |
| language | English |
| last_indexed | 2024-03-09T01:39:50Z |
| publishDate | 2023-03-01 |
| publisher | Compuscript Ltd |
| record_format | Article |
| series | Zoonoses |
| spelling | doaj.art-25e2018f50834540866d7cd28ce1bb802023-12-08T17:00:44ZengCompuscript LtdZoonoses2737-74662737-74742023-03-013198110.15212/ZOONOSES-2022-0050Purified Immunoglobulin F(ab′) 2 Protects Mice and Rhesus Monkeys against Lethal Ricin IntoxicationJingjing TianCong LiBochang ShiHui HanYuan LiuLingyun TanKeyu WangFang YanWei HeBo LiNaxin ZhengHuabin LiXinyu LiChongyu TianYuanqiang ZhengZhongpeng ZhaoRuiwen FanRicin is a highly toxic ribosome-inactivating lectin derived from castor beans. To date, no antidote is available to treat ricin-poisoned patients, and the development of a safe and effective antidote is urgently needed. First, ricin was prepared and used to construct a mouse model and a rhesus monkey model of ricin intoxication. Second, pepsin-digested F(ab′) 2 fragments of serum IgG from horses injected with Freund’s-adjuvanted purified ricin were prepared. Third, the protective efficacy was evaluated in mouse and rhesus monkey models of lethal ricin intoxication. The purity quotient of the prepared ricin and F(ab′) 2 fragments exceeded 90% and 85% in the mouse and monkey models, respectively. The LD 50 of ricin in mice and rhesus monkeys was 2.7 and 9 μg/kg, respectively. A quantity of 6.25 and 1.85 mg/kg F(ab′) 2 was sufficient to treat lethal ricin intoxication in the mice and rhesus monkeys, respectively. Finally, the effect of this therapeutic antibody on peripheral blood immune cells was examined by analysis of peripheral blood immune cells through single cell sequencing. The underlying mechanism was found to involve restraining neutrophil activation, proliferation, and differentiation. Purified F(ab′) 2 fragments administered with needle-free devices fully protect mice and rhesus monkeys against lethal doses of ricin intoxication.https://www.scienceopen.com/hosted-document?doi=10.15212/ZOONOSES-2022-0050 |
| spellingShingle | Jingjing Tian Cong Li Bochang Shi Hui Han Yuan Liu Lingyun Tan Keyu Wang Fang Yan Wei He Bo Li Naxin Zheng Huabin Li Xinyu Li Chongyu Tian Yuanqiang Zheng Zhongpeng Zhao Ruiwen Fan Purified Immunoglobulin F(ab′) 2 Protects Mice and Rhesus Monkeys against Lethal Ricin Intoxication Zoonoses |
| title | Purified Immunoglobulin F(ab′) 2 Protects Mice and Rhesus Monkeys against Lethal Ricin Intoxication |
| title_full | Purified Immunoglobulin F(ab′) 2 Protects Mice and Rhesus Monkeys against Lethal Ricin Intoxication |
| title_fullStr | Purified Immunoglobulin F(ab′) 2 Protects Mice and Rhesus Monkeys against Lethal Ricin Intoxication |
| title_full_unstemmed | Purified Immunoglobulin F(ab′) 2 Protects Mice and Rhesus Monkeys against Lethal Ricin Intoxication |
| title_short | Purified Immunoglobulin F(ab′) 2 Protects Mice and Rhesus Monkeys against Lethal Ricin Intoxication |
| title_sort | purified immunoglobulin f ab 2 protects mice and rhesus monkeys against lethal ricin intoxication |
| url | https://www.scienceopen.com/hosted-document?doi=10.15212/ZOONOSES-2022-0050 |
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