| Autor: |
Manocha N; Amity Institute of Virology & Immunology, Amity University Uttar Pradesh, Sector-125, Noida 201313, Uttar Pradesh, India.; Centre International de Recherche en Infectiologie, Université de Lyon, INSERM U1111, CNRS UMR 5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, 69364 Lyon, France.; Virology Unit, Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, Delhi, India., Laubreton D; Centre International de Recherche en Infectiologie, Université de Lyon, INSERM U1111, CNRS UMR 5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, 69364 Lyon, France., Robert X; Molecular Microbiology and Structural Biochemistry, UMR 5086 CNRS Université de Lyon, 7 Passage du Vercors, CEDEX 07, 69367 Lyon, France., Marvel J; Centre International de Recherche en Infectiologie, Université de Lyon, INSERM U1111, CNRS UMR 5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, 69364 Lyon, France., Gueguen-Chaignon V; Protein Science Facility, Université Claude Bernard Lyon 1, CNRS UAR3444, INSERM US8, Ecole Normale Supérieure de Lyon, SFR Biosciences, 69007 Lyon, France., Gouet P; Molecular Microbiology and Structural Biochemistry, UMR 5086 CNRS Université de Lyon, 7 Passage du Vercors, CEDEX 07, 69367 Lyon, France., Kumar P; Amity Institute of Virology & Immunology, Amity University Uttar Pradesh, Sector-125, Noida 201313, Uttar Pradesh, India., Khanna M; Virology Unit, Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, Delhi, India. |
| Abstrakt: |
Dengue virus (DENV) infection continues to be a public health challenge, lacking a specific cure. Vaccination remains the primary strategy against dengue; however, existing live-attenuated vaccines display variable efficacy across four serotypes, influenced by host serostatus and age, and predominantly inducing humoral responses. To address this limitation, this study investigates a multiepitope-based immunogen designed to induce robust cellular immunity across all DENV serotypes. The chimeric immunogen integrates H-2 d specific MHC-I binding T-cell epitopes derived from conserved domains within the DENV envelope protein. Immuno-informatics analyses supported its stability, non-allergenic nature, and strong MHC-I binding affinity as an antigen. To assess the immunogenicity of the multiepitope, it was expressed in murine bone-marrow-derived dendritic cells (BMDCs) that were used to prime mice. In this experimental model, simultaneous exposure to T-cell epitopes from all four DENV serotypes initiated distinct IFNγ-CD8 T-cell responses for different serotypes. These results supported the potential of the multiepitope construct as a vaccine candidate. While the optimization of the immunogen design remains a continuous pursuit, this proof-of-concept study provides a starting point for evaluating its protective efficacy against dengue infection in vivo. Moreover, our results support the development of a multiepitope vaccine that could trigger a pan-serotype anti-dengue CD8 response. |
