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

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 predominan...

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Published inVaccines (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
LanguageEnglish
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
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Abstract 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.
AbstractList 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.
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.
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[sup.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.
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-2d 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.
Audience Academic
Author Gueguen-Chaignon, Virginie
Gouet, Patrice
Laubreton, Daphné
Manocha, Nilanshu
Kumar, Prashant
Khanna, Madhu
Marvel, Jacqueline
Robert, Xavier
AuthorAffiliation 2 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; daphne.laubreton@inserm.fr (D.L.); jacqueline.marvel@inserm.fr (J.M.)
1 Amity Institute of Virology & Immunology, Amity University Uttar Pradesh, Sector-125, Noida 201313, Uttar Pradesh, India; nilanshu.manocha@student.amity.edu (N.M.); pkumar18@amity.edu (P.K.)
3 Virology Unit, Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, Delhi, India
5 Protein Science Facility, Université Claude Bernard Lyon 1, CNRS UAR3444, INSERM US8, Ecole Normale Supérieure de Lyon, SFR Biosciences, 69007 Lyon, France; virginie.gueguen-chaignon@ibcp.fr
4 Molecular Microbiology and Structural Biochemistry, UMR 5086 CNRS Université de Lyon, 7 Passage du Vercors, CEDEX 07, 69367 Lyon, France; xavier.robert@ibcp.fr (X.R.); patrice.gouet@ibcp.fr (P.G.)
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– name: 4 Molecular Microbiology and Structural Biochemistry, UMR 5086 CNRS Université de Lyon, 7 Passage du Vercors, CEDEX 07, 69367 Lyon, France; xavier.robert@ibcp.fr (X.R.); patrice.gouet@ibcp.fr (P.G.)
– name: 1 Amity Institute of Virology & Immunology, Amity University Uttar Pradesh, Sector-125, Noida 201313, Uttar Pradesh, India; nilanshu.manocha@student.amity.edu (N.M.); pkumar18@amity.edu (P.K.)
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Issue 3
Keywords vaccine candidate
cellular immunity
immunization
multiepitope vaccine
MHC I-binding epitopes
dengue virus
cross-serotype protection
memory T cells
Language English
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Snippet Dengue virus (DENV) infection continues to be a public health challenge, lacking a specific cure. Vaccination remains the primary strategy against dengue;...
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SubjectTerms 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
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Title Unveiling a Shield of Hope: A Novel Multiepitope-Based Immunogen for Cross-Serotype Cellular Defense against Dengue Virus
URI https://www.ncbi.nlm.nih.gov/pubmed/38543950
https://www.proquest.com/docview/3003822667/abstract/
https://search.proquest.com/docview/3014003069
https://pubmed.ncbi.nlm.nih.gov/PMC10975250
https://doaj.org/article/9ea3161905ed48c4890a8d143a0651a8
Volume 12
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