Lipid-nanoparticle-encapsulated mRNA vaccines induce protective memory CD8 T cells against a lethal viral infection.

Autor:	Knudson CJ; Department of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA., Alves-Peixoto P; Department of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga 4710-057, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4806-909, Portugal., Muramatsu H; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Stotesbury C; Department of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA., Tang L; Department of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA., Lin PJC; Acuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada., Tam YK; Acuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada., Weissman D; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Pardi N; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Sigal LJ; Department of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: luis.sigal@jefferson.edu.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2021 Sep 01; Vol. 29 (9), pp. 2769-2781. Date of Electronic Publication: 2021 May 14.
DOI:	10.1016/j.ymthe.2021.05.011
Abstrakt:	It is well established that memory CD8 T cells protect susceptible strains of mice from mousepox, a lethal viral disease caused by ectromelia virus (ECTV), the murine counterpart to human variola virus. While mRNA vaccines induce protective antibody (Ab) responses, it is unknown whether they also induce protective memory CD8 T cells. We now show that immunization with different doses of unmodified or N(1)-methylpseudouridine-modified mRNA (modified mRNA) in lipid nanoparticles (LNP) encoding the ECTV gene EVM158 induced similarly strong CD8 T cell responses to the epitope TSYKFESV, albeit unmodified mRNA-LNP had adverse effects at the inoculation site. A single immunization with 10 μg modified mRNA-LNP protected most susceptible mice from mousepox, and booster vaccination increased the memory CD8 T cell pool, providing full protection. Moreover, modified mRNA-LNP encoding TSYKFESV appended to green fluorescent protein (GFP) protected against wild-type ECTV infection while lymphocytic choriomeningitis virus glycoprotein (GP) modified mRNA-LNP protected against ECTV expressing GP epitopes. Thus, modified mRNA-LNP can be used to create protective CD8 T cell-based vaccines against viral infections. (Copyright © 2021 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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