Enhanced Assessment of Cross-Reactive Antigenic Determinants within the Spike Protein

• Published in: International journal of molecular sciences Vol. 25; no. 15; p. 8180
• Main Authors: Lechuga, Guilherme C, Temerozo, Jairo R, Napoleão-Pêgo, Paloma, Carvalho, João P R S, Gomes, Larissa R, Bou-Habib, Dumith Chequer, Morel, Carlos M, Provance, Jr, David W, Souza, Thiago M L, De-Simone, Salvatore G
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.08.2024
• Subjects: Amino acids; Antibodies; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antibody-Dependent Enhancement - immunology; antibody-mediated enhancement; Antigen-antibody reactions; Antigenic determinants; B-cell epitope; Brazil; Cell death; Comparative analysis; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - virology; COVID-19 vaccines; Cross Reactions - immunology; Dengue - immunology; Dengue - virology; Dengue fever; Dengue virus; Dengue Virus - immunology; Dengue viruses; Enzyme-linked immunosorbent assay; Epidemics; Epitopes, B-Lymphocyte - immunology; Humans; Immunodominant Epitopes - immunology; Infection; Infections; Mutation; Pandemics; Peptides; Proteins; SARS-CoV-2 - immunology; SARS-CoV-2 variants; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - immunology; spike protein; Vaccination; Vaccines; Viral antibodies; Viral infections; Viruses; West Nile virus; Brazil; COVID-19; spike protein; SARS-CoV-2 variants; antibody-mediated enhancement; Dengue virus; B-cell epitope; vaccination
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25158180

Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses regarding SARS-CoV-2 infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear B-cell epitopes in its spike glycoprotein with an SPOT synthesis peptide array probed with a pool of serum from hospitalized COVID-19 patients. The bioinformatics showed a restricted set of epitopes unique to SARS-CoV-2 compared to other coronavirus family members. Potential crosstalk was also detected with Dengue virus (DENV), which was confirmed by screening individuals infected with DENV before the COVID-19 pandemic in a commercial ELISA for anti-SARS-CoV-2 antibodies. A high-resolution evaluation of antibody reactivity against peptides representing epitopes in the spike protein identified ten sequences in the NTD, RBD, and S2 domains. Functionally, antibody-dependent enhancement (ADE) in SARS-CoV-2 infections of monocytes was observed in vitro with pre-pandemic Dengue-positive sera. A significant increase in viral load was measured compared to that of the controls, with no detectable neutralization or considerable cell death, suggesting its role in viral entry. Cross-reactivity against peptides from spike proteins was observed for the pre-pandemic sera. This study highlights the importance of identifying specific epitopes generated during the humoral response to a pathogenic infection to understand the potential interplay of previous and future infections on diseases and their impact on vaccinations and immunodiagnostics.