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Improved control of SARS-CoV-2 by treatment with nucleocapsid-specific monoclonal antibody

Dangi, Tanushree, Sanchez, Sarah, Class, Jacob, Richner, Michelle C., Visvabharathy, Lavanya, Chung, Young Rock, Bentley, Kirsten ORCID:, Stanton, Richard J. ORCID:, Koralnik, Igor J., Richner, Justin M. and Penaloza-MacMaster, Pablo 2022. Improved control of SARS-CoV-2 by treatment with nucleocapsid-specific monoclonal antibody. Journal of Clinical Investigation 132 (23) , e162282. 10.1172/JCI162282

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The SARS-CoV-2 spike protein is the main antigen in all approved COVID-19 vaccines and is also the only target for monoclonal antibody 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 interrogate whether nucleocapsid-specific antibodies can improve protection against SARSCoV-2. We first immunized mice with a nucleocapsid-based vaccine, and then transferred sera from these mice into naïve mice, followed by challenge with SARS-CoV-2. We show that mice that received nucleocapsid-specific sera or a nucleocapsid-specific monoclonal antibody (mAb) exhibited enhanced control of SARS-CoV-2. Nucleocapsid-specific antibodies elicited NK-mediated antibodydependent cellular cytotoxicity (ADCC) against infected cells. 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 monoclonal antibody therapies to treat COVID-19.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Publisher: American Society for Clinical Investigation
ISSN: 1558-8238
Funders: MRC
Date of First Compliant Deposit: 17 October 2022
Date of Acceptance: 5 October 2022
Last Modified: 25 May 2023 19:00

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