دورية أكاديمية
mRNA-LNP vaccine-induced CD8 + T cells protect mice from lethal SARS-CoV-2 infection in the absence of specific antibodies.
| العنوان: | mRNA-LNP vaccine-induced CD8 + T cells protect mice from lethal SARS-CoV-2 infection in the absence of specific antibodies. |
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| المؤلفون: | Montoya B; Department of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA., Melo-Silva CR; 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., Kafle S; Department of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA., Lidskiy P; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA., Bajusz C; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; National Laboratory for Biotechnology, Institute of Genetics, HUN-REN Biological Research Centre, Szeged, Hungary., Vadovics M; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Muramatsu H; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Abraham E; National Laboratory for Biotechnology, Institute of Genetics, HUN-REN Biological Research Centre, Szeged, Hungary; MTA SZBK Lendület Laboratory of Cell Cycle Regulation, Synthetic and Systems Biology Unit, Institute of Biochemistry, HUN-REN Biological Research Centre, Szeged, Hungary., Lipinszki Z; National Laboratory for Biotechnology, Institute of Genetics, HUN-REN Biological Research Centre, Szeged, Hungary; MTA SZBK Lendület Laboratory of Cell Cycle Regulation, Synthetic and Systems Biology Unit, Institute of Biochemistry, HUN-REN Biological Research Centre, Szeged, Hungary., Chatterjee D; Department of Neurosciences, Thomas Jefferson University Vickie and Jack Farber Institute for Neuroscience, Philadelphia, PA, USA., Scher G; Department of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA., Benitez J; Department of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA., Sung MMH; Acuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada., Tam YK; Acuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada., Catanzaro NJ; Department of Epidemiology, Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Schäfer A; Department of Epidemiology, Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Andino R; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA., Baric RS; Department of Epidemiology, Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Martinez DR; Department of Immunobiology, Center for Infection and Immunity, Yale School of Medicine, New Haven, CT 06520, USA., Pardi N; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: pnorbert@pennmedicine.upenn.edu., Sigal LJ; Department of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: luis.sigal@jefferson.edu. |
| المصدر: | Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2024 Jun 05; Vol. 32 (6), pp. 1790-1804. Date of Electronic Publication: 2024 Apr 11. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 100890581 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-0024 (Electronic) Linking ISSN: 15250016 NLM ISO Abbreviation: Mol Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : Cambridge, MA : Cell Press Original Publication: San Diego, CA : Academic Press, 2000- |
| مواضيع طبية MeSH: | CD8-Positive T-Lymphocytes*/immunology , SARS-CoV-2*/immunology , COVID-19*/immunology , COVID-19*/prevention & control , Spike Glycoprotein, Coronavirus*/immunology , Spike Glycoprotein, Coronavirus*/genetics , COVID-19 Vaccines*/immunology , Antibodies, Viral*/immunology, Animals ; Mice ; Female ; Male ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal |
| مستخلص: | The role of CD8 + T cells in SARS-CoV-2 pathogenesis or mRNA-LNP vaccine-induced protection from lethal COVID-19 is unclear. Using mouse-adapted SARS-CoV-2 virus (MA30) in C57BL/6 mice, we show that CD8 + T cells are unnecessary for the intrinsic resistance of female or the susceptibility of male mice to lethal SARS-CoV-2 infection. Also, mice immunized with a di-proline prefusion-stabilized full-length SARS-CoV-2 Spike (S-2P) mRNA-LNP vaccine, which induces Spike-specific antibodies and CD8 + T cells specific for the Spike-derived VNFNFNGL peptide, are protected from SARS-CoV-2 infection-induced lethality and weight loss, while mice vaccinated with mRNA-LNPs encoding only VNFNFNGL are protected from lethality but not weight loss. CD8 + T cell depletion ablates protection in VNFNFNGL but not in S-2P mRNA-LNP-vaccinated mice. Therefore, mRNA-LNP vaccine-induced CD8 + T cells are dispensable when protective antibodies are present but essential for survival in their absence. Hence, vaccine-induced CD8 + T cells may be critical to protect against SARS-CoV-2 variants that mutate epitopes targeted by protective antibodies. Competing Interests: Declaration of interests L.J.S. is a member of the Scientific Advisory Board of RNA Advanced Technologies member. N.P. is named on patents describing the use of nucleoside-modified mRNA in LNPs as a vaccine platform. He has disclosed those interests fully to the University of Pennsylvania and has an approved plan for managing potential conflicts arising from licensing those patents. N.P. served on the mRNA strategic advisory board of Sanofi Pasteur in 2022 and Pfizer in 2023–2024, and is a member of the Scientific Advisory Board of AldexChem and BioNet and has consulted for Vaccine Company Inc. and Pasture Bio. R.S.B. is a member of the Scientific Advisory Board of Invivyd and VaxArt and has consulted on virus-related countermeasures with Gilead, Moderna, Takeda, BioNet, and Jenssen Bio unrelated to this project. Y.K.T. and M.M.H. Sung are employees of Acuitas Therapeutics. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
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| معلومات مُعتمدة: | R01 AI169460 United States AI NIAID NIH HHS; R01 AI175567 United States AI NIAID NIH HHS; R56 AI110457 United States AI NIAID NIH HHS; T32 AI134646 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: CD8 T cells; SARS-CoV-2; antibodies; mRNA-LNP vaccines; mice |
| المشرفين على المادة: | 0 (Spike Glycoprotein, Coronavirus) 0 (COVID-19 Vaccines) 0 (Antibodies, Viral) 0 (spike protein, SARS-CoV-2) |
| تواريخ الأحداث: | Date Created: 20240412 Date Completed: 20240606 Latest Revision: 20240620 |
| رمز التحديث: | 20240620 |
| مُعرف محوري في PubMed: | PMC11184341 |
| DOI: | 10.1016/j.ymthe.2024.04.019 |
| PMID: | 38605519 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1525-0024 |
|---|---|
| DOI: | 10.1016/j.ymthe.2024.04.019 |