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Improved control of SARS-CoV-2 by treatment with a nucleocapsid-specific monoclonal antibody
Authors:Tanushree Dangi  Sarah Sanchez  Jacob Class  Michelle Richner  Lavanya Visvabharathy  Young Rock Chung  Kirsten Bentley  Richard J. Stanton  Igor J. Koralnik  Justin M. Richner  Pablo Penaloza-MacMaster
Affiliation:1.Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.;2.Department of Microbiology and Immunology, University of Illinois College of Medicine at Chicago, Chicago, Illinois, USA.;3.Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.;4.Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Abstract:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main antigen in all approved COVID-19 vaccines and is also the only target for monoclonal antibody (mAb) therapies. Immune responses to other viral antigens are generated after SARS-CoV-2 infection, but their contribution to the antiviral response remains unclear. Here, we interrogated whether nucleocapsid-specific antibodies can improve protection against SARS-CoV-2. We first immunized mice with a nucleocapsid-based vaccine and then transferred sera from these mice into naive mice, followed by challenge with SARS-CoV-2. We show that mice that received nucleocapsid-specific sera or a nucleocapsid-specific mAb exhibited enhanced control of SARS-CoV-2. Nucleocapsid-specific antibodies elicited NK-mediated, antibody-dependent cellular cytotoxicity (ADCC) against infected cells. To our knowledge, these findings provide the first demonstration in the coronavirus literature that antibody responses specific to the nucleocapsid protein can improve viral clearance, providing a rationale for the clinical evaluation of nucleocapsid-based mAb therapies to treat COVID-19.
Keywords:COVID-19   Immunology
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