An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV.

Autor: Guo H; IGM Biosciences, Mountain View, CA, USA., Cho B; IGM Biosciences, Mountain View, CA, USA., Hinton PR; IGM Biosciences, Mountain View, CA, USA., He S; IGM Biosciences, Mountain View, CA, USA., Yu Y; IGM Biosciences, Mountain View, CA, USA., Ramesh AK; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA., Sivaccumar JP; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA., Ku Z; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA., Campo K; IGM Biosciences, Mountain View, CA, USA., Holland S; IGM Biosciences, Mountain View, CA, USA., Sachdeva S; IGM Biosciences, Mountain View, CA, USA., Mensch C; IGM Biosciences, Mountain View, CA, USA., Dawod M; IGM Biosciences, Mountain View, CA, USA., Whitaker A; Cellular, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT, USA.; Department of Medicine, Division of Pulmonary Disease and Critical Care Medicine, University of Vermont, Burlington, VT, USA., Eisenhauer P; Department of Medicine, Division of Pulmonary Disease and Critical Care Medicine, University of Vermont, Burlington, VT, USA., Falcone A; Department of Medicine, Division of Pulmonary Disease and Critical Care Medicine, University of Vermont, Burlington, VT, USA., Honce R; Department of Medicine, Division of Pulmonary Disease and Critical Care Medicine, University of Vermont, Burlington, VT, USA., Botten JW; Department of Medicine, Division of Pulmonary Disease and Critical Care Medicine, University of Vermont, Burlington, VT, USA.; Department of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, VT, USA., Carroll SF; IGM Biosciences, Mountain View, CA, USA., Keyt BA; IGM Biosciences, Mountain View, CA, USA., Womack AW; IGM Biosciences, Mountain View, CA, USA., Strohl WR; IGM Biosciences, Mountain View, CA, USA., Xu K; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA., Zhang N; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA., An Z; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA., Ha S; IGM Biosciences, Mountain View, CA, USA., Shiver JW; IGM Biosciences, Mountain View, CA, USA., Fu TM; IGM Biosciences, Mountain View, CA, USA.
Jazyk: angličtina
Zdroj: Emerging microbes & infections [Emerg Microbes Infect] 2023 Dec; Vol. 12 (2), pp. 2275598. Date of Electronic Publication: 2023 Dec 11.
DOI: 10.1080/22221751.2023.2275598
Abstrakt: The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by its high neutralization potency against all known SARS-CoV-2 variants, including Omicron BQ.1, BQ.1.1, XBB.1 and XBB.1.5. In addition, it demonstrates potency against SARS-CoV-1, human NL63, as well as bat and pangolin CoVs. The multivalent trap is effective in both prophylactic and therapeutic settings since a single intranasal dosing confers protection in human ACE2 transgenic mice against viral challenges. Lastly, this molecule is stable at ambient temperature for more than twelve weeks and can sustain physical stress from aerosolization. These results demonstrate the potential of a decameric ACE2 viral trap as an inhalation solution for ACE2-dependent coronaviruses of current and future pandemic concerns.
Databáze: MEDLINE