1. Immunogenicity and crossreactivity of antibodies to the nucleocapsid protein of SARS-CoV-2: utility and limitations in seroprevalence and immunity studies
- Author
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Rubén López-Aladid, Luis Izquierdo, Francisco Carmona-Torre, Gemma Moncunill, Ruth Aguilar, Antoni Torres, Carlo Carolis, Natalia Rodrigo Melero, Matija Popovic, Alberto L. García-Basteiro, Alfredo Mayor, Jordi Chi, Laia Fernández-Barat, Marta Vidal, Carlota Dobaño, Alfons Jiménez, Marta Tortajada, Gabriel Reina, and Rebeca Santano
- Subjects
Male ,0301 basic medicine ,MFI, median fluorescence intensity ,Rhinovirus ,viruses ,LOESS, locally estimated scatterplot smoothing ,Antibodies, Viral ,medicine.disease_cause ,0302 clinical medicine ,Seroepidemiologic Studies ,FL, full-length ,skin and connective tissue diseases ,COVID-19, coronavirus disease 2019 ,biology ,Immunogenicity ,RBD, receptor-binding domain ,virus diseases ,Common cold ,General Medicine ,CT, C-terminus ,030220 oncology & carcinogenesis ,ADE, antibody-dependent disease enhancement ,Female ,Antibody ,S, spike ,Alpha (ethology) ,Cross Reactions ,SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 ,Article ,rRT-PCR, real-time reverse-transcriptase polymerase chain reaction ,NT, N-terminus ,03 medical and health sciences ,Immunity ,Physiology (medical) ,medicine ,Coronavirus Nucleocapsid Proteins ,Humans ,Seroprevalence ,Biochemistry, medical ,SARS-CoV-2 ,M, month ,fungi ,Biochemistry (medical) ,Public Health, Environmental and Occupational Health ,COVID-19 ,HCoV, common cold human coronavirus ,medicine.disease ,Virology ,body regions ,030104 developmental biology ,Immunoglobulin G ,biology.protein ,N, nucleocapsid - Abstract
COVID-19 patients elicit strong responses to the nucleocapsid (N) protein of SARS-CoV-2 but binding antibodies are also detected in prepandemic individuals, indicating potential crossreactivity with common cold human coronaviruses (HCoV) and questioning its utility in seroprevalence studies. We investigated the immunogenicity of the full-length and shorter fragments of the SARS-CoV-2 N protein, and the crossreactivity of antibodies with HCoV. We identified a C-terminus region in SARS-CoV2 N of minimal sequence homology with HCoV that was more specific for SARS-CoV-2 and highly immunogenic. IgGs to the full-length SARS-CoV-2 N also recognized N229E N, and IgGs to HKU1 N recognized SARS-CoV-2 N. Crossreactivity with SARS-CoV-2 was stronger for alpha- rather than beta-HCoV despite having less sequence identity, revealing the importance of conformational recognition. Higher preexisting IgG to OC43 N correlated with lower IgG to SARS-CoV-2 N in rRT-PCR negative individuals, reflecting less exposure and indicating a potential protective association. Antibodies to SARS-CoV-2 N were higher in patients with more severe and longer duration of symptoms and in females. IgGs remained stable for at least 3 months, while IgAs and IgMs declined faster. In conclusion, N protein is a primary target of SARS-CoV-2-specific and HCoV crossreactive antibodies, both of which may affect the acquisition of immunity to COVID-19.
- Published
- 2021