Unveiling a Shield of Hope: A Novel Multiepitope-Based Immunogen for Cross-Serotype Cellular Defense against Dengue Virus

• Published in: Vaccines (Basel) Vol. 12; no. 3; p. 316
• Main Authors: Manocha, Nilanshu, Laubreton, Daphné, Robert, Xavier, Marvel, Jacqueline, Gueguen-Chaignon, Virginie, Gouet, Patrice, Kumar, Prashant, Khanna, Madhu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2024; MDPI
• Subjects: Antibodies; Antigens; Binding; Bone marrow; CD8 antigen; Cell-mediated immunity; cellular immunity; Control; cross-serotype protection; Dendritic cells; Dengue fever; dengue virus; Dengue viruses; Design optimization; Disease prevention; Effectiveness; Env protein; Epitopes; Global health; immunization; Immunogenetics; Immunogenicity; Infections; Informatics; ISO standards; Lymphocytes; Lymphocytes T; Major histocompatibility complex; MHC I-binding epitopes; multiepitope vaccine; Peptides; Proteins; Proteomics; Public health; Serotypes; Stability analysis; Testing; Total quality; Vaccines; Vector-borne diseases; Viral envelope proteins; Viruses; γ-Interferon; India; France; United States > US; vaccine candidate; cellular immunity; immunization; multiepitope vaccine; MHC I-binding epitopes; dengue virus; cross-serotype protection; memory T cells
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines12030316

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 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.