{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T08:56:57Z","timestamp":1765961817519,"version":"build-2065373602"},"reference-count":88,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro\/FAPERJ","award":["#110.198-13","#210.003\/2018","#467.488\/2014-2","301744\/2019-0","#03\/11"],"award-info":[{"award-number":["#110.198-13","#210.003\/2018","#467.488\/2014-2","301744\/2019-0","#03\/11"]}]},{"name":"Brazilian Council for Scientific Research","award":["#110.198-13","#210.003\/2018","#467.488\/2014-2","301744\/2019-0","#03\/11"],"award-info":[{"award-number":["#110.198-13","#210.003\/2018","#467.488\/2014-2","301744\/2019-0","#03\/11"]}]},{"name":"Mercosur Structural Convergence Fund","award":["#110.198-13","#210.003\/2018","#467.488\/2014-2","301744\/2019-0","#03\/11"],"award-info":[{"award-number":["#110.198-13","#210.003\/2018","#467.488\/2014-2","301744\/2019-0","#03\/11"]}]},{"name":"National Institutes of Science and Technology Program","award":["#110.198-13","#210.003\/2018","#467.488\/2014-2","301744\/2019-0","#03\/11"],"award-info":[{"award-number":["#110.198-13","#210.003\/2018","#467.488\/2014-2","301744\/2019-0","#03\/11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms25158180","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T14:39:08Z","timestamp":1722004748000},"page":"8180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Enhanced Assessment of Cross-Reactive Antigenic Determinants within the Spike Protein"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4538-3802","authenticated-orcid":false,"given":"Guilherme C.","family":"Lechuga","sequence":"first","affiliation":[{"name":"Center for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswald Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"},{"name":"Cellular Ultrastructure Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8092-2149","authenticated-orcid":false,"given":"Jairo R.","family":"Temerozo","sequence":"additional","affiliation":[{"name":"Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"},{"name":"National Institute for Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paloma","family":"Napole\u00e3o-P\u00eago","sequence":"additional","affiliation":[{"name":"Center for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswald Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o P. R. S.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Center for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswald Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"},{"name":"Graduate Program in Science and Biotechnology, Department of Molecular and Cellular Biology, Biology Institute, Fluminense Federal University, Niter\u00f3i 24220-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7194-0858","authenticated-orcid":false,"given":"Larissa R.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Center for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswald Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0552-9045","authenticated-orcid":false,"given":"Dumith Chequer","family":"Bou-Habib","sequence":"additional","affiliation":[{"name":"Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"},{"name":"National Institute for Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2752-0009","authenticated-orcid":false,"given":"Carlos M.","family":"Morel","sequence":"additional","affiliation":[{"name":"Center for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswald Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9824-0672","authenticated-orcid":false,"suffix":"Jr.","given":"David W.","family":"Provance","sequence":"additional","affiliation":[{"name":"Center for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswald Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago M. L.","family":"Souza","sequence":"additional","affiliation":[{"name":"Center for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswald Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"},{"name":"Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-656X","authenticated-orcid":false,"given":"Salvatore G.","family":"De-Simone","sequence":"additional","affiliation":[{"name":"Center for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswald Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"},{"name":"Graduate Program in Science and Biotechnology, Department of Molecular and Cellular Biology, Biology Institute, Fluminense Federal University, Niter\u00f3i 24220-900, Brazil"},{"name":"Epidemiology and Molecular Systematics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2313","DOI":"10.1002\/rmv.2313","article-title":"Covid-19 vaccines and variants of concern: A review","volume":"32","year":"2022","journal-title":"Rev. Med. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/s41586-021-04388-0","article-title":"Striking antibody evasion manifested by the omicron variant of SARS-CoV-2","volume":"602","author":"Liu","year":"2022","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.cell.2021.12.032","article-title":"The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic","volume":"185","author":"Hoffmann","year":"2022","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1016\/j.cell.2021.03.013","article-title":"Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity","volume":"184","author":"Lam","year":"2021","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100189","DOI":"10.1016\/j.xcrm.2020.100189","article-title":"Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses","volume":"2","author":"Ladner","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Devaux, C.A., and Fantini, J. (2023). Unravelling antigenic cross-reactions toward the world of coronaviruses: Extent of the stability of shared epitopes and SARS-CoV-2 anti-spike cross-neutralizing antibodies. Pathogens, 12.","DOI":"10.3390\/pathogens12050713"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"20383","DOI":"10.1038\/s41598-021-99642-w","article-title":"Immunodominant linear B cell epitopes in the spike and membrane proteins of SARS-CoV-2 identified by immunoinformatics prediction and immunoassay","volume":"11","author":"Polyiam","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cheng, Y.L., Chao, C.H., Lai, Y.C., Hsieh, K.H., Wang, J.R., Wan, S.W., Huang, H.J., Chuang, Y.C., Chuang, W.J., and Yeh, T.M. (2022). Antibodies against the SARS-CoV-2 S1-RBD cross-react with dengue virus and hinder dengue pathogenesis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.941923"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/s41577-022-00809-x","article-title":"The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses","volume":"23","author":"Murray","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/rmv.405","article-title":"Antibody-dependent enhancement of viral infection: Molecular mechanisms and in vivo implications","volume":"13","author":"Takada","year":"2003","journal-title":"Rev. Med. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1089\/088282403763635465","article-title":"Antibody-dependent enhancement of virus infection and disease","volume":"16","author":"Tirado","year":"2003","journal-title":"Viral Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.molimm.2022.11.010","article-title":"Antibody-Dependent Enhancement (ADE) and the role of complement system in disease pathogenesis","volume":"152","author":"Thomas","year":"2022","journal-title":"Mol. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"421","DOI":"10.2174\/1570162X113116660062","article-title":"Antibody-dependent enhancement and the risk of HIV infection","volume":"11","author":"Gorlani","year":"2013","journal-title":"Curr. HIV Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6332","DOI":"10.1128\/JVI.72.8.6332-6338.1998","article-title":"Determinants of human immunodeficiency virus type 1 envelope glycoprotein activation by soluble CD4 and monoclonal antibodies","volume":"72","author":"Sullivan","year":"1998","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1128\/JVI.76.6.2827-2834.2002","article-title":"Antibody-mediated enhancement of human immunodeficiency virus type 1 infectivity is determined by the structure of gp120 and depends on modulation of the gp120-CCR5 interaction","volume":"76","author":"Guillon","year":"2002","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1016\/S0140-6736(07)61687-0","article-title":"Dengue","volume":"370","author":"Halstead","year":"2007","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"108699","DOI":"10.1016\/j.celrep.2021.108699","article-title":"Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associate with distinct epitopes on the RBD","volume":"34","author":"Zhou","year":"2021","journal-title":"Cell Rep."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Okuya, K., Hattori, T., Saito, T., Takadate, Y., Sasaki, M., Furuyama, W., Marzi, A., Ohiro, Y., Konno, S., and Hattori, T. (2022). Multiple routes of antibody-dependent enhancement of SARS-CoV-2 infection. Microbiol. Spectr., 10.","DOI":"10.1128\/spectrum.01553-21"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9422","DOI":"10.1073\/pnas.0703498104","article-title":"Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention","volume":"104","author":"Goncalvez","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.chom.2007.03.002","article-title":"The stoichiometry of antibody-mediated neutralization and enhancement of West Nile virus infection","volume":"1","author":"Pierson","year":"2007","journal-title":"Cell Host Microbe"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/imr.12367","article-title":"Fc receptors in antibody-dependent enhancement of viral infections","volume":"268","author":"Taylor","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mu, S., Song, S., Hao, Y., Luo, F., Wu, R., Wang, Y., Han, X., Li, T., Hu, C., and Li, S. (2022). Neutralizing antibodies from the rare convalescent donors elicited antibody-dependent enhancement of SARS-CoV-2 variants infection. Front. Med., 9.","DOI":"10.3389\/fmed.2022.952697"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/s41586-020-2538-8","article-title":"A perspective on potential antibody-dependent enhancement of SARS-CoV-2","volume":"584","author":"Arvin","year":"2020","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"155256","DOI":"10.1016\/j.cyto.2020.155256","article-title":"ADE and hyperinflammation in SARS-CoV2 infection\u2014Comparison with dengue hemorrhagic fever and feline infectious peritonitis","volume":"136","author":"Cloutier","year":"2020","journal-title":"Cytokine"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yang, Y., and Xu, F. (2022). Evolving understanding of antibody-dependent enhancement (ADE) of SARS-CoV-2. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1008285"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41586-020-2349-y","article-title":"Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody","volume":"583","author":"Pinto","year":"2020","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"108737","DOI":"10.1016\/j.celrep.2021.108737","article-title":"Cross-reactivity of SARS-CoV structural protein antibodies against SARS-CoV-2","volume":"34","author":"Bates","year":"2021","journal-title":"Cell Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1038\/s41467-020-15562-9","article-title":"Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV","volume":"11","author":"Ou","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1953683","DOI":"10.1080\/19420862.2021.1953683","article-title":"Characterization of MW06, a human monoclonal antibody with cross-neutralization activity against both SARS-CoV-2 and SARS-CoV","volume":"13","author":"Jiang","year":"2021","journal-title":"MAbs"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Watanabe, Y., Hosokawa, N., Yoshida, M., Miura, T., and Kawano, M. (2023). Identification of closed linear epitopes in S1-RBD and S2-HR1\/2 of SARS-CoV-2 spike protein able to induce neutralizing Abs. Vaccines, 11.","DOI":"10.3390\/vaccines11020287"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1007\/s10875-021-00997-6","article-title":"Serologic cross-reactivity of SARS-CoV-2 with endemic and seasonal betacoronaviruses","volume":"41","author":"Hicks","year":"2021","journal-title":"J. Clin. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1002\/eji.202049101","article-title":"Peptide microarray-based analysis of antibody responses to SARS-CoV-2 identifies unique epitopes with potential for diagnostic test development","volume":"51","author":"Holenya","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, Z., Ren, L., Hao, Y., Zhu, M., Jiang, H., Wang, S., Li, D., and Shao, Y. (2022). Pre-existing anti-HCoV-OC43 immunity influences the durability and cross-reactivity of humoral response to SARS-CoV-2 vaccination. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.978440"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1126\/science.abe1107","article-title":"Preexisting and de novo humoral immunity to SARS-CoV-2 in humans","volume":"370","author":"Ng","year":"2020","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e111","DOI":"10.1016\/S2666-5247(20)30053-7","article-title":"Seroprevalence of SARS-CoV-2 in Hong Kong and in residents evacuated from Hubei province, China: A multicohort study","volume":"1","author":"To","year":"2020","journal-title":"Lancet Microbe"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Khan, A.A., Alahmari, A.A., Almuzaini, Y., Alamri, F., Alsofayan, Y.M., Aburas, A., Al-Muhsen, S., Van Kerkhove, M., Yezli, S., and Ciottone, G.R. (2021). Potential cross-reactive immunity to COVID-19 infection in individuals with laboratory-confirmed MERS-CoV infection: A national retrospective cohort study from Saudi Arabia. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.727989"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"eabe9950","DOI":"10.1126\/sciimmunol.abe9950","article-title":"Cross-reactive antibodies against human coronaviruses and the animal coronavirome suggest diagnostics for future zoonotic spillovers","volume":"6","author":"Klompus","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wang, J., Guo, C., Cai, L., Liao, C., Yi, H., Li, Q., Hu, H., Deng, Q., Lu, Y., and Guo, Z. (2021). Pre-existing cross-reactive antibody responses do not significantly impact inactivated COVID-19 vaccine-induced neutralization. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.772511"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e146316","DOI":"10.1172\/jci.insight.146316","article-title":"A majority of uninfected adults show preexisting antibody reactivity against SARS-CoV-2","volume":"6","author":"Majdoubi","year":"2021","journal-title":"JCI Insight"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Rak, A., Donina, S., Zabrodskaya, Y., Rudenko, L., and Isakova-Sivak, I. (2022). Cross-reactivity of SARS-CoV-2 nucleocapsid-binding antibodies and its implication for COVID-19 serology tests. Viruses, 14.","DOI":"10.3390\/v14092041"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Souris, M., Tshilolo, L., Parzy, D., Ingoba, L.L., Ntoumi, F., Kamgaing, R., Ndour, M., Mbongi, D., Phoba, B., and Tshilolo, M.A. (2022). Pre-pandemic cross-reactive immunity against SARS-CoV-2 among Central and West African populations. Viruses, 14.","DOI":"10.3390\/v14102259"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/s41598-023-27810-1","article-title":"Linear epitope mapping of the humoral response against SARS-CoV-2 in two independent African cohorts","volume":"13","author":"Spadoni","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Haynes, W.A., Kamath, K., Bozekowski, J., Baum-Jones, E., Campbell, M., Casanovas-Massana, A., Daugherty, P.S., Dela Cruz, C.S., Dhal, A., and Farhadian, S.F. (2021). High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19. Commun. Biol., 4.","DOI":"10.1038\/s42003-021-02835-2"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Camerini, D., Randall, A.Z., Trappl-Kimmons, K., Oberai, A., Hung, C., Edgar, J., Shandling, A., Huynh, V., Teng, A.A., and Hermanson, G. (2021). Mapping SARS-CoV-2 antibody epitopes in COVID-19 patients with a multi-coronavirus protein microarray. Microbiol. Spectr., 9.","DOI":"10.1128\/Spectrum.01416-21"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"De-Simone, S.G., Napole\u00e3o-P\u00eago, P., Lechuga, G.C., Carvalho, J.P.R.S., Monteiro, M.E., Morel, C.M., and Provance, D.W. (2023). Mapping IgA epitope and cross-reactivity between Severe acute Respiratory Syndrome-Associated Coronavirus 2 and DENV. Vaccines, 11.","DOI":"10.3390\/vaccines11121749"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Lorenz, P., Steinbeck, F., Mai, F., Reisinger, E.C., and M\u00fcller-Hilke, B. (2023). A linear B-cell epitope close to the furin cleavage site within the S1 domain of SARS-CoV-2 Spike protein discriminates the humoral immune response of nucleic acid- and protein-based vaccine cohorts. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1192395"},{"key":"ref_47","first-page":"111022","article-title":"COVID-19 vaccination elicits an evolving, cross- reactive antibody response to epitopes conserved with endemic coronavirus spike proteins","volume":"40","author":"Elko","year":"2022","journal-title":"CellReports"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41586-023-05697-2","article-title":"Spike and nsp6 are key determinants of SARS-CoV-2 Omicron BA.1 attenuation","volume":"615","author":"Chen","year":"2023","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1039\/D1NR03831A","article-title":"Recent advances in nanotechnology-based COVID-19 vaccines and therapeutic antibodies","volume":"14","author":"Du","year":"2022","journal-title":"Nanoscale"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/s41577-022-00784-3","article-title":"Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses","volume":"23","author":"Chen","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1080\/22221751.2022.2125348","article-title":"Structure-based neutralizing mechanisms for SARS-CoV-2 antibodies","volume":"11","author":"Huang","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.cell.2020.09.037","article-title":"Mapping neutralizing and immunodominant sites on the SARS-CoV-2 Spike receptor-binding domain by structure-guided high-resolution serology","volume":"183","author":"Piccoli","year":"2020","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.molimm.2022.10.016","article-title":"Identification of virus-specific B-cell epitopes by convalescent plasma from COVID-19 patients","volume":"152","author":"Wang","year":"2022","journal-title":"Mol. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wang, C.Y., Peng, W.J., Kuo, B.S., Ho, Y.H., Wang, M.S., Yang, Y.T., Chang, P.Y., Shen, Y.H., and Hwang, K.P. (2023). Toward a pan-SARS-CoV-2 vaccine targeting conserved epitopes on Spike and non-spike proteins for potent, broad and durable immune responses. PLoS Pathog., 19.","DOI":"10.1371\/journal.ppat.1010870"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e2215628119","DOI":"10.1073\/pnas.2204256119","article-title":"The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2","volume":"119","author":"Xiong","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"AlKhalifah, J.M., Seddiq, W., Alshehri, M.A., Alhetheel, A., Albarrag, A., Meo, S.A., Al-Tawfiq, J.A., and Barry, M. (2023). Impact of MERS-CoV and SARS-CoV-2 viral infection on immunoglobulin-IgG cross-reactivity. Vaccines, 11.","DOI":"10.3390\/vaccines11030552"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1038\/s41467-022-32262-8","article-title":"SARS-CoV-2 variants of concern: Spike protein mutational analysis and epitope for broad neutralization","volume":"13","author":"Mannar","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Prakash, S., Dhanushkodi, N.R., Zayou, L., Ibraim, I.C., Quadiri, A., Coulon, P.G., Tifrea, D.F., Suzer, B., Shaik, A.M., and Chilukuri, A. (2024). Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1328905"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"eabn8897","DOI":"10.1126\/science.abn8897","article-title":"Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529","volume":"376","author":"Zhou","year":"2022","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Shrestha, L.B., Tedla, N., and Bull, R.A. (2021). Broadly neutralizing antibodies against emerging SARS-CoV-2 variants. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.752003"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1126\/science.abj3321","article-title":"Broad betacoronavirus neutralization by a stem helix\u2013specific human antibody","volume":"373","author":"Pinto","year":"2021","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1126\/science.abq2679","article-title":"ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies","volume":"377","author":"Low","year":"2022","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1126\/science.abq3773","article-title":"Broadly neutralizing antibodies target the coronavirus fusion peptide","volume":"377","author":"Dacon","year":"2022","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"eabd4250","DOI":"10.1126\/science.abd4250","article-title":"Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity","volume":"370","author":"Shrock","year":"2022","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"16817","DOI":"10.1038\/s41598-022-20849-6","article-title":"Differential patterns of cross-reactive antibody response against SARS-CoV-2 spike protein detected for chronically ill and healthy COVID-19 na\u00efve individuals","volume":"12","author":"Jaago","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1139\/cjm-2020-0572","article-title":"Dengue virus: Epidemiology, biology, and disease etiology","volume":"67","author":"Roy","year":"2021","journal-title":"Can. J. Microbiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1002\/jmv.25646","article-title":"Dengue proteins with their role in pathogenesis, and strategies for developing an effective anti-dengue treatment: A review","volume":"92","author":"Nasar","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Vanroye, F., Bossche, D.V.D., Brosius, I., Tack, B., Esbroeck, M.V., and Jacobs, J. (2021). COVID-19 antibody detecting rapid diagnostic tests show high cross-reactivity when challenged with pre-pandemic malaria, schistosomiasis, and dengue samples. Diagnostics, 11.","DOI":"10.3390\/diagnostics11071163"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1159\/000522479","article-title":"Low Risk of Serological Cross-Reactivity between the Dengue Virus and SARS-CoV-2-IgG antibodies using advanced detection assays","volume":"65","author":"Shurrab","year":"2022","journal-title":"Intervirology"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Hunsawong, T., Buddhari, D., Rungrojcharoenkit, K., Suthangkornkul, R., Mongkolsirichaikul, D., Lohachanakul, J., Tayong, K., Sirikajornpan, K., Rodpradit, P., and Poolpanichupatam, Y. (2022). Anti-Arbovirus Antibodies Cross-React With Severe Acute Respiratory Syndrome Coronavirus 2. Microbiol. Spectr., 10.","DOI":"10.1128\/spectrum.02639-22"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"540","DOI":"10.3390\/idr13020050","article-title":"Potential misdiagnosis between COVID-19 and dengue infection using rapid serological test","volume":"13","author":"Khairunisa","year":"2021","journal-title":"Infect. Dis. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/s41577-020-00434-6","article-title":"Immunological considerations for COVID-19 vaccine strategies","volume":"20","author":"Jeyanathan","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Nath, H., Mallick, A., Roy, S., Sukla, S., Basu, K., De, A., and Biswas, S. (2021). Archived dengue serum samples produced false-positive results in SARS-CoV-2 lateral flow-based rapid antibody tests. J. Med. Microbiol., 70.","DOI":"10.1099\/jmm.0.001369"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1126\/science.aan6836","article-title":"Antibody-dependent enhancement of severe dengue disease in humans","volume":"358","author":"Katzelnick","year":"2017","journal-title":"Science"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"12354","DOI":"10.1038\/s41598-021-91793-0","article-title":"Antibody-dependent enhancement representing in vitro infective progeny virus titer correlates with the viremia level in dengue patients","volume":"11","author":"Yamanaka","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1056\/NEJMoa1800820","article-title":"Effect of dengue serostatus on dengue vaccine safety and efficacy","volume":"379","author":"Sridhar","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Matveeva, O., Nechipurenko, Y., Lagutkin, D., Yegorov, Y.E., and Kzhyshkowska, J. (2022). SARS-CoV-2 infection of phagocytic immune cells and COVID-19 pathology: Antibody-dependent as well as independent cell entry. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1050478"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41586-022-04702-4","article-title":"Fc\u03b3R-mediated SARS-CoV-2 infection of monocytes activates inflammation","volume":"606","author":"Junqueira","year":"2022","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Nakayama, E.E., and Shioda, T. (2023). SARS-CoV-2 Related antibody-dependent enhancement phenomena in vitro and in vivo. Microorganisms, 11.","DOI":"10.3390\/microorganisms11041015"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Wang, S., Wang, J., Yu, X., Jiang, W., Chen, S., Wang, R., Wang, M., Jiao, S., Yang, Y., and Wang, W. (2022). Antibody-dependent enhancement (ADE) of SARS-CoV-2 pseudoviral infection requires Fc\u03b3RIIB and virus-antibody complex with bivalent interaction. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-03207-0"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/s41745-021-00268-8","article-title":"Neutralizing antibodies and antibody-dependent enhancement in COVID-19: A perspective","volume":"102","author":"Ajmeriya","year":"2022","journal-title":"J. Indian. Inst. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4203","DOI":"10.1016\/j.cell.2021.06.021","article-title":"In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies","volume":"184","author":"Li","year":"2021","journal-title":"Cell"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Matveev, A., Pyankov, O., Khlusevich, Y., Tyazhelkova, O., Emelyanova, L., Timofeeva, A., Shipovalov, A., Chechushkov, A., Zaitseva, N., and Kudrov, G. (2023). Antibodies Capable of Enhancing SARS-CoV-2 Infection Can Circulate in Patients with Severe COVID-19. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310799"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e29628","DOI":"10.1002\/jmv.29628","article-title":"Antibody-dependent enhancement (ADE) of SARS-CoV-2 in patients exposed to MERS-CoV and SARS-CoV-2 antigens","volume":"96","author":"Thomas","year":"2024","journal-title":"J. Med. Virol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1016\/j.vaccine.2023.03.005","article-title":"Antibody-dependent disease enhancement (ADE) after COVID-19 vaccination and beta-glucans as a safer strategy in management","volume":"41","author":"Ikewaki","year":"2023","journal-title":"Vaccine"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"De-Simone, S.G., Gomes, L.R., Napole\u00e3o-P\u00eago, P., Lechuga, G.C., Pina, J.C., and Silva, F.R. (2021). Identification of linear B epitopes liable for the protective immunity of diphtheria toxin. Vaccines, 9.","DOI":"10.3390\/vaccines9040313"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Monteiro, M.E.S., Lechuga, G.C., Napole\u00e3o-P\u00eago, P., Carvalho, J.P.R.S., Gomes, L.R., Morel, C.M., Provance, D.W., and De-Simone, S.G. (2024). Humoral immune response to SARS-CoV-2 spike protein receptor-binding motif linear epitopes. Vaccines, 12.","DOI":"10.20944\/preprints202402.0093.v1"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX: Structure visualization for researchers, educators, and developers","volume":"30","author":"Pettersen","year":"2021","journal-title":"Protein Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8180\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:24:26Z","timestamp":1760109866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,26]]},"references-count":88,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158180"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158180","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,7,26]]}}}