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J Clin Invest . Improved control of SARS-CoV-2 by treatment with nucleocapsid-specific monoclonal antibody

tetano

Editor, Senior Moderator
J Clin Invest


. 2022 Oct 11;e162282.
doi: 10.1172/JCI162282. Online ahead of print.
Improved control of SARS-CoV-2 by treatment with nucleocapsid-specific monoclonal antibody


Tanushree Dangi[SUP] 1 [/SUP], Sarah Sanchez[SUP] 1 [/SUP], Jacob Class[SUP] 2 [/SUP], Michelle C Richner[SUP] 2 [/SUP], Lavanya Visvabharathy[SUP] 1 [/SUP], Young Rock Chung[SUP] 1 [/SUP], Kirsten Bentley[SUP] 3 [/SUP], Richard J Stanton[SUP] 3 [/SUP], Igor J Koralnik[SUP] 4 [/SUP], Justin M Richner[SUP] 2 [/SUP], Pablo Penaloza-MacMaster[SUP] 5 [/SUP]



Affiliations

Abstract

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.

Keywords: Adaptive immunity; COVID-19; Immunology.
 
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