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

tetano

Editor, Senior Moderator
Immunol Res


. 2026 May 7;74(1):52.
doi: 10.1007/s12026-026-09783-1.
Fine specificity of antibodies to SARS-CoV-2 nucleoprotein in patients with COVID-19

Caterina Porciani[SUP] 1 [/SUP], Francesco Pisani[SUP] 2 [/SUP], Maria Laura Manca[SUP] 1 [/SUP], Lorenzo Pacini[SUP] 3 [/SUP], Fosca Errante[SUP] 3 [/SUP], Roberto Mozzo[SUP] 4 [/SUP], Luigi De Simone[SUP] 4 [/SUP], Paola Migliorini[SUP] 1 [/SUP], Federico Pratesi[SUP] 5 [/SUP]


Affiliations
Abstract

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 (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 PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB] (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, 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.

Keywords: Anti-nucleocapsid antibodies; Antibody avidity; COVID-19; Epitope mapping; Nucleocapsid.

 
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