Enhanced mucosal antibody- and T-cell responses against SARS-CoV-2 after heterologous intramuscular mRNA prime/intranasal protein boost vaccination with a combination adjuvant.

Autor:	Laghlali G; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Wiest MJ; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA., Karadag D; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA., Warang P; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., O'Konek JJ; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA., Chang LA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Park S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Yan V; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Farazuddin M; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA., Janczak KW; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA., García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Baker JR Jr; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA., Wong PT; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: ptw@umich.edu., Schotsaert M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: ptw@umich.edu.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2024 Oct 25. Date of Electronic Publication: 2024 Oct 25.
DOI:	10.1016/j.ymthe.2024.10.016
Abstrakt:	Current COVID-19 mRNA vaccines delivered intramuscularly (IM) induce effective systemic immunity, but with suboptimal immunity at mucosal sites, limiting their ability to impart sterilizing immunity. There is strong interest in rerouting immune responses induced in the periphery by parenteral vaccination to the portal entry site of respiratory viruses, such as SARS-CoV-2, by mucosal vaccination. We previously demonstrated the combination adjuvant, NE/IVT, consisting of a nanoemulsion (NE) and an RNA-based RIG-I agonist (IVT) induces potent systemic and mucosal immune responses in protein-based SARS-CoV-2 vaccines administered intranasally (IN). Herein, we demonstrate priming IM with mRNA followed by heterologous IN boosting with NE/IVT adjuvanted recombinant antigen induces strong mucosal and systemic antibody responses and enhances antigen-specific T cell responses in mucosa-draining lymph nodes compared to IM/IM and IN/IN prime/boost regimens. While all regimens induced cross-neutralizing antibodies against divergent variants and sterilizing immunity in the lungs of challenged mice, mucosal vaccination, either as homologous prime/boost or heterologous IN boost after IM mRNA prime was required to impart sterilizing immunity in the upper respiratory tract. Our data demonstrate the benefit of hybrid regimens whereby strong immune responses primed via IM vaccination are rerouted by IN vaccination to mucosal sites to provide optimal protection to SARS-CoV-2. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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