{"id":44970,"date":"2025-10-09T00:47:02","date_gmt":"2025-10-08T22:47:02","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/10\/09\/non-neutralizing-antibodies-against-sars-cov-2-nucleocapsid-protein-mediate-variant-transcendent-antibody-dependent-cellular-cytotoxicity\/"},"modified":"2025-10-09T00:47:02","modified_gmt":"2025-10-08T22:47:02","slug":"non-neutralizing-antibodies-against-sars-cov-2-nucleocapsid-protein-mediate-variant-transcendent-antibody-dependent-cellular-cytotoxicity","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/10\/09\/non-neutralizing-antibodies-against-sars-cov-2-nucleocapsid-protein-mediate-variant-transcendent-antibody-dependent-cellular-cytotoxicity\/","title":{"rendered":"Non-neutralizing antibodies against SARS-CoV-2 nucleocapsid protein mediate variant transcendent antibody-dependent cellular cytotoxicity"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Oct 8:vkaf123. doi: 10.1093\/jimmun\/vkaf123. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Vaccination strategies and correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly focused on the spike (S) protein and neutralizing antibodies. However, the rapid emergence of SARS-CoV-2 variants has reduced the effectiveness of spike-based vaccines and monoclonal antibodies. It remains unclear how non-neutralizing antibodies that target the nucleocapsid (N) protein contribute to protection against SARS-CoV-2 variants, especially their ability to trigger antibody effector functions. These antibodies may function by binding to infected cells and initiating antibody-dependent cellular cytotoxicity (ADCC), eliminating infected cells. In this study, we demonstrate that antibodies from individuals who recovered from coronavirus disease 2019 (COVID-19) infection and\/or were vaccinated with the S protein vaccine recognize viral proteins on the surface of infected cells and mediate ADCC-mediated NK cell killing of infected cells. Notably, non-neutralizing antibodies induced in COVID-19 infection recognized non-spike proteins on the surface of SARS-CoV-2 variant-infected cells, and these non-neutralizing antibodies cleared SARS-CoV-2 infected cells following depletion of spike antibodies. We identified N and minimal membrane (M) proteins as the targets of non-neutralizing antibodies on the surface of these variant-infected cells. We show that enriched N-specific antibodies from individuals who recovered from COVID-19 infection more consistently killed SARS-CoV-2 variant-infected cells than antibodies to the spike protein. The observed cross-reactivity and robust ADCC activity mediated by N-specific antibodies across various SARS-CoV-2 variant-infected cells highlight the N protein as an important vaccine target in addition to the S protein. Targeting N may provide more comprehensive and durable immunity against SARS-CoV-2 and its evolving variants.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41060789\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20251008184701&amp;v=2.18.0.post9+e462414\">41060789<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf123\">10.1093\/jimmun\/vkaf123<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Oct 8:vkaf123. doi: 10.1093\/jimmun\/vkaf123. Online ahead of print. ABSTRACT Vaccination strategies and correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly focused on the spike (S) protein and neutralizing antibodies. However, the rapid emergence of SARS-CoV-2 variants has reduced the effectiveness of spike-based vaccines and monoclonal antibodies. It &#8230; <a title=\"Non-neutralizing antibodies against SARS-CoV-2 nucleocapsid protein mediate variant transcendent antibody-dependent cellular cytotoxicity\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/10\/09\/non-neutralizing-antibodies-against-sars-cov-2-nucleocapsid-protein-mediate-variant-transcendent-antibody-dependent-cellular-cytotoxicity\/\" aria-label=\"Read more about Non-neutralizing antibodies against SARS-CoV-2 nucleocapsid protein mediate variant transcendent antibody-dependent cellular cytotoxicity\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-44970","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/44970","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=44970"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/44970\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=44970"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=44970"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=44970"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}