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 6

Nucleocapsid-specific mAb improves the control of SARS-CoV-2 infection.

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Nucleocapsid-specific mAb improves the control of SARS-CoV-2 infection. ...
(A) Experimental approach for evaluating viral control after treatment with a nucleocapsid-specific mAb during a low-dose viral challenge. mAbs (800 μg, IgG control or anti-N) were injected intraperitoneally into naive K18-hACE2 mice. On the following day, the K18-hACE2 mice were challenged intranasally with 103 PFU SARS-CoV-2. (B) Weight loss following infection. (C) Viral loads in lungs as determined by RT-qPCR. RNA was harvested from the lungs on post-infection day 7, and viral RNA was quantified. (D) Experimental approach for evaluating viral control after treatment with a nucleocapsid-specific mAb during a high-dose viral challenge. mAbs (800 μg, IgG control or anti-N) were injected intraperitoneally into naive K18-hACE2 mice. On the following day, the K18-hACE2 mice were challenged intranasally with 5 × 104 PFU SARS-CoV-2. (E) Weight loss following infection. (F) Viral loads in lungs as determined by RT-qPCR. RNA was harvested from the lungs on post-infection day 5, and viral RNA was quantified. (G) IL-6 levels in sera. (H and I) H&E-stained images of lung. Scale bars: 100 μm. Data in A–C are from low-dose viral challenges, and data in D–I are from high-dose viral challenges. Challenges were performed with a total of 4–5 mice per group in BSL-3 facilities. P values were calculated using a Mann-Whitney U test. Error bars represent the SEM.