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

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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03245739
Contributor : Tineke Cantaert <>
Submitted on : Wednesday, June 2, 2021 - 7:08:38 AM
Last modification on : Wednesday, June 9, 2021 - 3:33:55 AM
Long-term archiving on: : Friday, September 3, 2021 - 6:18:44 PM

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Distributed under a Creative Commons Attribution 4.0 International License

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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, Frontiers, 2019, 10, pp.1424. ⟨10.3389/fimmu.2019.01424⟩. ⟨pasteur-03245739⟩

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