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

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

doi:10.1172/JCI162282

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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

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.

Original language	English (US)
Article number	e162282
Journal	Journal of Clinical Investigation
Volume	132
Issue number	23
DOIs	https://doi.org/10.1172/JCI162282
State	Published - Dec 1 2022

Funding

We thank Thomas Gallagher, Oscar Aguilar, David Masopust, and Vaiva Vezys for discussions and reagents. This work was made possible by grants from the National Institute of Allergy and Infectious Diseases (NIAID), NIH (to JMR); the National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH (U54 EB027049, to PPM); the National Institute on Drug Abuse (NIDA), NIH (DP2DA051912, to PPM).

ASJC Scopus subject areas

General Medicine

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1172/JCI162282

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title = "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.",

author = "Tanushree Dangi and Sarah Sanchez and Jacob Class and Michelle Richner and Lavanya Visvabharathy and Chung, {Young Rock} and Kirsten Bentley and Stanton, {Richard J.} and Koralnik, {Igor J.} and Richner, {Justin M.} and Pablo Penaloza-MacMaster",

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

Abstract

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UN SDGs

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