Therapeutic Effects of Monoclonal Antibody against Dengue Virus NS1 in a STAT1 Knockout Mouse Model of Dengue Infection
| Autor: | Pei Wei Chen, Chin Yu Chen, Robert Anderson, Betty A. Wu-Hsieh, Jessica Lin, Han Lee, Yen Chung Lai, Trai Ming Yeh, Chia Yi Hung, Chiou Feng Lin, Tzong Shiann Ho, Ya Ting Chu, Yee Shin Lin, Ching Chuan Liu, Yung Chun Chuang, Chien-Kuo Lee, Hsuan Franziska Wu, Shu Wen Wan, Chih Peng Chang, Shuying Wang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.drug_class viruses medicine.medical_treatment 030106 microbiology Immunology Hemorrhage Dengue virus Biology Cross Reactions Viral Nonstructural Proteins Monoclonal antibody medicine.disease_cause Autoantigens Epitope Virus Dengue fever Dengue 03 medical and health sciences Epitopes Mice medicine Immunology and Allergy Animals Humans Cells Cultured Encephalitis Virus Japanese Mice Knockout Mice Inbred BALB C Mice Inbred C3H Antibody-Dependent Cell Cytotoxicity virus diseases Antibodies Monoclonal Immunotherapy biochemical phenomena metabolism and nutrition Japanese encephalitis Dengue Virus medicine.disease Virology Recombinant Proteins Disease Models Animal 030104 developmental biology STAT1 Transcription Factor Immunization |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 199(8) |
| ISSN: | 1550-6606 |
| Popis: | Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome and is endemic to tropical and subtropical regions of the world. Our previous studies showed the existence of epitopes in the C-terminal region of DENV nonstructural protein 1 (NS1) which are cross-reactive with host Ags and trigger anti–DENV NS1 Ab–mediated endothelial cell damage and platelet dysfunction. To circumvent these potentially harmful events, we replaced the C-terminal region of DENV NS1 with the corresponding region from Japanese encephalitis virus NS1 to create chimeric DJ NS1 protein. Passive immunization of DENV-infected mice with polyclonal anti–DJ NS1 Abs reduced viral Ag expression at skin inoculation sites and shortened DENV-induced prolonged bleeding time. We also investigated the therapeutic effects of anti-NS1 mAb. One mAb designated 2E8 does not recognize the C-terminal region of DENV NS1 in which host–cross-reactive epitopes reside. Moreover, mAb 2E8 recognizes NS1 of all four DENV serotypes. We also found that mAb 2E8 caused complement-mediated lysis in DENV-infected cells. In mouse model studies, treatment with mAb 2E8 shortened DENV-induced prolonged bleeding time and reduced viral Ag expression in the skin. Importantly, mAb 2E8 provided therapeutic effects against all four serotypes of DENV. We further found that mAb administration to mice as late as 1 d prior to severe bleeding still reduced prolonged bleeding time and hemorrhage. Therefore, administration with a single dose of mAb 2E8 can protect mice against DENV infection and pathological effects, suggesting that NS1-specific mAb may be a therapeutic option against dengue disease. |
| Databáze: | OpenAIRE |
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