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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.
Afiliación
  • Kao YS; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
  • Yu CY; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 701, Taiwan.
  • Huang HJ; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
  • Tien SM; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
  • Wang WY; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
  • Yang M; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
  • Anderson R; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
  • Yeh TM; Canadian Center for Vaccinology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
  • Lin YS; Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
  • Wan SW; Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; and.
J Immunol ; 203(7): 1909-1917, 2019 10 01.
Article en En | MEDLINE | ID: mdl-31451673
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD4-Positivos / Inmunización / Proteínas no Estructurales Virales / Linfocitos T CD8-positivos / Dengue / Virus del Dengue / Vacunas contra el Dengue / Inmunidad Celular / Anticuerpos Antivirales Límite: Animals Idioma: En Revista: J Immunol Año: 2019 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD4-Positivos / Inmunización / Proteínas no Estructurales Virales / Linfocitos T CD8-positivos / Dengue / Virus del Dengue / Vacunas contra el Dengue / Inmunidad Celular / Anticuerpos Antivirales Límite: Animals Idioma: En Revista: J Immunol Año: 2019 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos