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

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 contr...

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Published inThe Journal of clinical investigation Vol. 132; no. 23
Main Authors Dangi, Tanushree, Sanchez, Sarah, Class, Jacob, Richner, Michelle, Visvabharathy, Lavanya, Chung, Young Rock, Bentley, Kirsten, Stanton, Richard J, Koralnik, Igor J, Richner, Justin M, Penaloza-MacMaster, Pablo
Format Journal Article
LanguageEnglish
Published United States American Society for Clinical Investigation 01.12.2022
Subjects
Animals
Antibodies, Monoclonal - pharmacology
Antibodies, Viral
COVID-19
COVID-19 - therapy
COVID-19 Vaccines
Immune response
Immunological research
Immunology
Mice
Monoclonal antibodies
Nucleocapsid - immunology
SARS-CoV-2
Spike Glycoprotein, Coronavirus - immunology
United States
COVID-19
Adaptive immunity
Immunology
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Summary: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.
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ISSN:1558-8238
0021-9738
1558-8238
DOI:10.1172/JCI162282