Combination of modified NS1 and NS3 as a novel vaccine strategy against dengue virus infection

Yu San Kao, Chia Yi Yu, Hong Jyun Huang, Sen Mao Tien, Wan Yu Wang, Martyr Yang, Robert Anderson, Trai Ming Yeh, Yee Shin Lin, Shu Wen Wan

研究成果: Article

摘要

Dengue virus (DENV) causes a range of illness, including dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. DENV nonstructural protein (NS) 1 has been considered to be a desirable vaccine candidate for its ability to induce Ab and complement-dependent cytolysis of DENV-infected cells as well as to block the pathogenic effects of NS1. However a potential drawback of NS1 as a vaccine is that anti-DENV NS1 Abs can lead to endothelial cell damage and platelet dysfunction by antigenic cross-reactivity. Therefore, we modified the DENV NS1 by replacing the C-terminal cross-reactive epitopes with the corresponding region of Japanese encephalitis virus NS1 to generate a chimeric DJ NS1 protein. Active immunization with DJ NS1 induced a strong Ab response. To enhance cellular immunity, we further combined DJ NS1 with DENV NS3 to immunize mice and showed activation of Ag-specific CD4+ and CD8+ T cells in addition to Ab responses. We further detected NS3-specific CTL activities as well as CD107a expression of effector cells. Importantly, the protective effects attributed by DJ NS1 and NS3 immunization were demonstrated in a DENV-infected mouse model by reduced viral titers, soluble NS1 levels, mouse tail bleeding time, and vascular leakage at skin injection sites. Collectively, the results from this study reveal the humoral and cellular immune responses and the protective effects conferred by DJ NS1 and NS3 immunization in the mouse model of DENV infection and provide a potential strategy for dengue vaccine design.

原文English
頁(從 - 到)1909-1917
頁數9
期刊Journal of Immunology
203
發行號7
DOIs
出版狀態Published - 2019 十月 1

指紋

Dengue Virus
Virus Diseases
Vaccines
Severe Dengue
Cellular Immunity
Japanese Encephalitis Virus
Immunization
Dengue Vaccines
Bleeding Time
Dengue
Humoral Immunity
Blood Vessels
Tail
Epitopes
Vaccination
Proteins
Blood Platelets
Endothelial Cells
T-Lymphocytes
Skin

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

引用此文

Kao, Y. S., Yu, C. Y., Huang, H. J., Tien, S. M., Wang, W. Y., Yang, M., ... Wan, S. W. (2019). Combination of modified NS1 and NS3 as a novel vaccine strategy against dengue virus infection. Journal of Immunology, 203(7), 1909-1917. https://doi.org/10.4049/jimmunol.1900136
Kao, Yu San ; Yu, Chia Yi ; Huang, Hong Jyun ; Tien, Sen Mao ; Wang, Wan Yu ; Yang, Martyr ; Anderson, Robert ; Yeh, Trai Ming ; Lin, Yee Shin ; Wan, Shu Wen. / Combination of modified NS1 and NS3 as a novel vaccine strategy against dengue virus infection. 於: Journal of Immunology. 2019 ; 卷 203, 編號 7. 頁 1909-1917.
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Kao, YS, Yu, CY, Huang, HJ, Tien, SM, Wang, WY, Yang, M, Anderson, R, Yeh, TM, Lin, YS & Wan, SW 2019, 'Combination of modified NS1 and NS3 as a novel vaccine strategy against dengue virus infection', Journal of Immunology, 卷 203, 編號 7, 頁 1909-1917. https://doi.org/10.4049/jimmunol.1900136

Combination of modified NS1 and NS3 as a novel vaccine strategy against dengue virus infection. / Kao, Yu San; Yu, Chia Yi; Huang, Hong Jyun; Tien, Sen Mao; Wang, Wan Yu; Yang, Martyr; Anderson, Robert; Yeh, Trai Ming; Lin, Yee Shin; Wan, Shu Wen.

於: Journal of Immunology, 卷 203, 編號 7, 01.10.2019, p. 1909-1917.

研究成果: Article

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AU - Kao, Yu San

AU - Yu, Chia Yi

AU - Huang, Hong Jyun

AU - Tien, Sen Mao

AU - Wang, Wan Yu

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AU - Yeh, Trai Ming

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AU - Wan, Shu Wen

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