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<p>The production of antibodies against viral structural proteins such as the spike (S) and the nucleocapsid (N) is a hallmark of SARS-CoV-2 infection. The N protein contains several immunogenic regions. In this work we analysed epitope specificity and avidity of anti-N antibodies in COVID-19 patients. Eighty-nine COVID-19 patients were recruited. IgG, IgA, IgM antibodies to recombinant N protein and to 6 different peptides containing predicted B epitopes were measured by ELISA. Antibody avidity was evaluated by chaotropic ELISA. Anti-N IgG, IgA, and IgM were detected in 59%, 41% and 30% respectively; in 11% cases anti-N IgG are the only antibodies present in COVID patients. IgG and IgA anti-N antibodies levels correlate with levels of IL-6 and inversely with PaO<sub>2</sub>/FiO<sub>2</sub> ratio (<i>p</i> &lt; 0,005). Anti-N IgG displayed medium avidity in 51% and high avidity in 49% COVID patients; anti-N avidity was negatively correlated with PaO<sub>2</sub>/FiO<sub>2</sub> (<i>p</i> &lt; 0,05). Median anti-N antibody levels were similar in discharged or deceased patients and antibody avidity was not correlated with outcome. Among peptides, N<sub>366−388</sub> is the most frequently recognized by IgG, IgA and IgM antibodies followed by N<sub>380−400</sub>, bound by patients IgG and IgA but anti-N<sub>380−400</sub> IgG display higher avidity than anti-N<sub>366−388</sub> IgG. These results indicate that anti-N antibodies are characterized by medium-high avidity and preferentially bind the COOH-terminus of the nucleoprotein. Anti-N antibodies, especially directed towards specific epitopes, might be relevant for the course of the infection, and their induction might improve current vaccination strategies.</p>

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Fine specificity of antibodies to SARS-CoV-2 nucleoprotein in patients with COVID-19

  • 期刊论文

  • 发表日期：

    2026年5月7日

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  • Caterina Porciani,
  • Francesco Pisani,
  • Maria Laura Manca,
  • Lorenzo Pacini,
  • Fosca Errante,
  • Roberto Mozzo,
  • Luigi De Simone,
  • Paola Migliorini,
  • Federico Pratesi

摘要

The production of antibodies against viral structural proteins such as the spike (S) and the nucleocapsid (N) is a hallmark of SARS-CoV-2 infection. The N protein contains several immunogenic regions. In this work we analysed epitope specificity and avidity of anti-N antibodies in COVID-19 patients. Eighty-nine COVID-19 patients were recruited. IgG, IgA, IgM antibodies to recombinant N protein and to 6 different peptides containing predicted B epitopes were measured by ELISA. Antibody avidity was evaluated by chaotropic ELISA. Anti-N IgG, IgA, and IgM were detected in 59%, 41% and 30% respectively; in 11% cases anti-N IgG are the only antibodies present in COVID patients. IgG and IgA anti-N antibodies levels correlate with levels of IL-6 and inversely with PaO2/FiO2 ratio (p < 0,005). Anti-N IgG displayed medium avidity in 51% and high avidity in 49% COVID patients; anti-N avidity was negatively correlated with PaO2/FiO2 (p < 0,05). Median anti-N antibody levels were similar in discharged or deceased patients and antibody avidity was not correlated with outcome. Among peptides, N366−388 is the most frequently recognized by IgG, IgA and IgM antibodies followed by N380−400, bound by patients IgG and IgA but anti-N380−400 IgG display higher avidity than anti-N366−388 IgG. These results indicate that anti-N antibodies are characterized by medium-high avidity and preferentially bind the COOH-terminus of the nucleoprotein. Anti-N antibodies, especially directed towards specific epitopes, might be relevant for the course of the infection, and their induction might improve current vaccination strategies.