期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 132, 期 23, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI162282
关键词
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资金
- National Institute of Allergy and Infectious Diseases (NIAID), NIH
- National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH [U54 EB027049]
- National Institute on Drug Abuse (NIDA), NIH [DP2DA051912]
This study demonstrates that nucleocapsid-specific antibodies can enhance control of SARS-CoV-2 infection and mediate antibody-dependent cellular cytotoxicity against infected cells. These findings provide a rationale for evaluating nucleocapsid-based monoclonal antibody therapies for the treatment of COVID-19.
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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