Improved control of SARS-CoV-2 by treatment with a nucleocapsid-specific monoclonal antibody
Tanushree Dangi, … , Justin M. Richner, Pablo Penaloza-MacMaster
Tanushree Dangi, … , Justin M. Richner, Pablo Penaloza-MacMaster
Published October 11, 2022
Citation Information: J Clin Invest. 2022;132(23):e162282. https://doi.org/10.1172/JCI162282.
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Research Article Immunology

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

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.

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

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Figure 7

N-specific antibodies bind to infected cells and trigger ADCC.

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N-specific antibodies bind to infected cells and trigger ADCC. (A) Repre...
(A) Representative FACS plots showing that N-specific sera and the N-specific mAb bound to SARS-CoV-2 infected cells. 293-ACE2 cells were infected with SARS-CoV-2, and binding to N-specific antibody was assessed by flow cytometry using a secondary antibody bound to Alexa Fluor 647. Control cells were mock infected. (B) N-specific antibodies triggered ADCC. 293-ACE2 cells were infected with SARS-CoV-2 and cocultured with effector cells (NKL-mCD16 cells), together with N-specific immune sera or anti-N mAb (clone 1C7). CD107a expression on NKL-mCD16 cells was quantified by flow cytometry after 5 hours. Data are from a 1:30 dilution, from 2 experiments, each with 5 per group. All data are shown. P values were calculated using a 2-way ANOVA with Dunnett’s multiple-comparison test. Error bars represent the SEM.