Evidence map›Paper›PMID 41060789›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2025

Non-neutralizing antibodies against SARS-CoV-2 nucleocapsid protein mediate variant transcendent antibody-dependent cellular cytotoxicity.

Anthonia E Osuagwu, Michael Payne, Jürgen Bosch, Uri Mbonye, Kien Nguyen, Jonathan Karn, Anna Bruchez, Christopher L King

Abstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Anthonia E OsuagwuDepartment of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, United States.ORCID 0000-0003-1245-6016
Michael PayneDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, United States.
Jürgen BoschDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, United States.ORCID 0000-0002-2624-4105
Uri MbonyeDepartment of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, United States.
Kien NguyenDepartment of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, United States.ORCID 0000-0002-7088-3457
Jonathan KarnDepartment of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, United States.ORCID 0000-0002-2900-094X
Anna BruchezDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, United States.
Christopher L KingDepartment of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, United States.ORCID 0000-0003-3873-7860

Funding

Early Drivers of Humoral Immunity to SARS-CoV-2 InfectionsU01CA260539 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI KING, CHRISTOPHER L · 2020 to 2024
$3.4M
National Institutes of Health (NIH) U01 CA260539-01NCI NIH HHS U01 CA260539NIH HHS U01 CA260539-01Nord Family Foundation
6 · The paper itself

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 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.

Indexed as

Antibodies, ViralAntibody-Dependent Cell CytotoxicityCoronavirus Nucleocapsid ProteinsCOVID-19PhosphoproteinsSARS-CoV-2Antibodies, NeutralizingCOVID-19 VaccinesFemaleHumansKiller Cells, NaturalSpike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralCoronavirus Nucleocapsid ProteinsCOVID-19 Vaccinesnucleocapsid phosphoprotein, SARS-CoV-2PhosphoproteinsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2antibody-dependent cellular cytotoxicitynonneutralizing antibodiesnucleocapsid ProteinSARS-CoV-2

Identifiers

PMID41060789
PMCPMC12614239

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.