Therapeutic efficacy of humanized monoclonal antibodies targeting dengue virus nonstructural protein 1 in the mouse model.
Dengue virus (DENV) which infects about 390 million people per year in tropical and subtropical areas manifests various disease symptoms, ranging from fever to life-threatening hemorrhage and even shock. To date, there is still no effective treatment for DENV disease, but only supportive care. DENV...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-04-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1010469 |
| _version_ | 1811306416145694720 |
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| author | Sen-Mao Tien Po-Chun Chang Yen-Chung Lai Yung-Chun Chuang Chin-Kai Tseng Yu-San Kao Hong-Jyun Huang Yu-Peng Hsiao Yi-Ling Liu Hsing-Han Lin Chien-Chou Chu Miao-Huei Cheng Tzong-Shiann Ho Chih-Peng Chang Shu-Fen Ko Che-Piao Shen Robert Anderson Yee-Shin Lin Shu-Wen Wan Trai-Ming Yeh |
| author_facet | Sen-Mao Tien Po-Chun Chang Yen-Chung Lai Yung-Chun Chuang Chin-Kai Tseng Yu-San Kao Hong-Jyun Huang Yu-Peng Hsiao Yi-Ling Liu Hsing-Han Lin Chien-Chou Chu Miao-Huei Cheng Tzong-Shiann Ho Chih-Peng Chang Shu-Fen Ko Che-Piao Shen Robert Anderson Yee-Shin Lin Shu-Wen Wan Trai-Ming Yeh |
| author_sort | Sen-Mao Tien |
| collection | DOAJ |
| description | Dengue virus (DENV) which infects about 390 million people per year in tropical and subtropical areas manifests various disease symptoms, ranging from fever to life-threatening hemorrhage and even shock. To date, there is still no effective treatment for DENV disease, but only supportive care. DENV nonstructural protein 1 (NS1) has been shown to play a key role in disease pathogenesis. Recent studies have shown that anti-DENV NS1 antibody can provide disease protection by blocking the DENV-induced disruption of endothelial integrity. We previously demonstrated that anti-NS1 monoclonal antibody (mAb) protected mice from all four serotypes of DENV challenge. Here, we generated humanized anti-NS1 mAbs and transferred them to mice after DENV infection. The results showed that DENV-induced prolonged bleeding time and skin hemorrhage were reduced, even several days after DENV challenge. Mechanistic studies showed the ability of humanized anti-NS1 mAbs to inhibit NS1-induced vascular hyperpermeability and to elicit Fcγ-dependent complement-mediated cytolysis as well as antibody-dependent cellular cytotoxicity of cells infected with four serotypes of DENV. These results highlight humanized anti-NS1 mAb as a potential therapeutic agent in DENV infection. |
| first_indexed | 2024-04-13T08:44:03Z |
| format | Article |
| id | doaj.art-1f07a1c790774ce6821a9e50ecdd9345 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-13T08:44:03Z |
| publishDate | 2022-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-1f07a1c790774ce6821a9e50ecdd93452022-12-22T02:53:45ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742022-04-01184e101046910.1371/journal.ppat.1010469Therapeutic efficacy of humanized monoclonal antibodies targeting dengue virus nonstructural protein 1 in the mouse model.Sen-Mao TienPo-Chun ChangYen-Chung LaiYung-Chun ChuangChin-Kai TsengYu-San KaoHong-Jyun HuangYu-Peng HsiaoYi-Ling LiuHsing-Han LinChien-Chou ChuMiao-Huei ChengTzong-Shiann HoChih-Peng ChangShu-Fen KoChe-Piao ShenRobert AndersonYee-Shin LinShu-Wen WanTrai-Ming YehDengue virus (DENV) which infects about 390 million people per year in tropical and subtropical areas manifests various disease symptoms, ranging from fever to life-threatening hemorrhage and even shock. To date, there is still no effective treatment for DENV disease, but only supportive care. DENV nonstructural protein 1 (NS1) has been shown to play a key role in disease pathogenesis. Recent studies have shown that anti-DENV NS1 antibody can provide disease protection by blocking the DENV-induced disruption of endothelial integrity. We previously demonstrated that anti-NS1 monoclonal antibody (mAb) protected mice from all four serotypes of DENV challenge. Here, we generated humanized anti-NS1 mAbs and transferred them to mice after DENV infection. The results showed that DENV-induced prolonged bleeding time and skin hemorrhage were reduced, even several days after DENV challenge. Mechanistic studies showed the ability of humanized anti-NS1 mAbs to inhibit NS1-induced vascular hyperpermeability and to elicit Fcγ-dependent complement-mediated cytolysis as well as antibody-dependent cellular cytotoxicity of cells infected with four serotypes of DENV. These results highlight humanized anti-NS1 mAb as a potential therapeutic agent in DENV infection.https://doi.org/10.1371/journal.ppat.1010469 |
| spellingShingle | Sen-Mao Tien Po-Chun Chang Yen-Chung Lai Yung-Chun Chuang Chin-Kai Tseng Yu-San Kao Hong-Jyun Huang Yu-Peng Hsiao Yi-Ling Liu Hsing-Han Lin Chien-Chou Chu Miao-Huei Cheng Tzong-Shiann Ho Chih-Peng Chang Shu-Fen Ko Che-Piao Shen Robert Anderson Yee-Shin Lin Shu-Wen Wan Trai-Ming Yeh Therapeutic efficacy of humanized monoclonal antibodies targeting dengue virus nonstructural protein 1 in the mouse model. PLoS Pathogens |
| title | Therapeutic efficacy of humanized monoclonal antibodies targeting dengue virus nonstructural protein 1 in the mouse model. |
| title_full | Therapeutic efficacy of humanized monoclonal antibodies targeting dengue virus nonstructural protein 1 in the mouse model. |
| title_fullStr | Therapeutic efficacy of humanized monoclonal antibodies targeting dengue virus nonstructural protein 1 in the mouse model. |
| title_full_unstemmed | Therapeutic efficacy of humanized monoclonal antibodies targeting dengue virus nonstructural protein 1 in the mouse model. |
| title_short | Therapeutic efficacy of humanized monoclonal antibodies targeting dengue virus nonstructural protein 1 in the mouse model. |
| title_sort | therapeutic efficacy of humanized monoclonal antibodies targeting dengue virus nonstructural protein 1 in the mouse model |
| url | https://doi.org/10.1371/journal.ppat.1010469 |
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