A Modified mRNA Vaccine Targeting Immunodominant NS Epitopes Protects Against Dengue Virus Infection in HLA Class I Transgenic Mice - Archive ouverte HAL Access content directly
Journal Articles Frontiers in Immunology Year : 2019

A Modified mRNA Vaccine Targeting Immunodominant NS Epitopes Protects Against Dengue Virus Infection in HLA Class I Transgenic Mice

(1) , (2) , (1) , (1) , (1) , (1) , (3) , (3) , (4) , (5) , (6) , (1) , (1)
1
2
3
4
5
6
Tineke Cantaert
  • Function : Correspondent author
  • PersonId : 1024674

Connectez-vous pour contacter l'auteur

Abstract

Dengue virus (DENV) induces strong T and B cell responses upon infection. Hence, it is difficult to determine the contribution of cell-mediated immunity alone in the long lasting protection against DENV infection and disease. Numerous CD4+ and CD8+ T cell epitopes have been identified, mainly in the non-structural proteins of DENV. Taking into account the immunogenicity and peptide sequence conservation among the different DENV serotypes, a minimal DENV antigen, called DENV1-NS, has been designed. This antigen is enriched in conserved and highly antigenic epitopes located in the NS3, NS4B, and NS5 regions of DENV1. To evaluate the ability of the DENV1-NS poly-epitope to express the antigenic peptides in the context of different HLA class I molecules, we established its in vivo immunogenicity by measuring, after DNA immunization and electroporation, the activation of DENV-specific CD8 T cells in transgenic mice expressing the human HLA-A*0201, -A*2402, -B*0702, and -B*3502 class I alleles. We then engineered a lipid nanoparticle (LNP) encapsulated modified mRNA vaccine encoding DENV1-NS and tested immunogenicity and protection in these human HLA class I transgenic mice, after transient blockade of the interferon (IFN) type I receptor. Significant protection was observed, after two injections of the mRNA vaccine. Collectively, these data strongly support the development of T cell-based vaccines targeting immunodominant T cell epitopes that generate potent virus-specific T cell responses conferring immunity against DENV infection.
Fichier principal
Vignette du fichier
fimmu-10-01424.pdf (2.88 Mo) Télécharger le fichier

Dates and versions

pasteur-03245739 , version 1 (02-06-2021)

Licence

Attribution - CC BY 4.0

Identifiers

Cite

Claude Roth, Tineke Cantaert, Chloé Colas, Matthieu Prot, Isabelle Casadémont, et al.. A Modified mRNA Vaccine Targeting Immunodominant NS Epitopes Protects Against Dengue Virus Infection in HLA Class I Transgenic Mice. Frontiers in Immunology, 2019, 10, pp.1424. ⟨10.3389/fimmu.2019.01424⟩. ⟨pasteur-03245739⟩
18 View
22 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More