{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Zayou L"],"funding":["NIAID NIH HHS"],"pubmed_abstract":["Since early 2020, several SARS-CoV-2 variants of concern (VOCs) continue to emerge, evading waning antibody mediated immunity produced by the current Spike-alone based COVID-19 vaccines. This caused a prolonged and persistent COVID-19 pandemic that is going to enter its fifth year. Thus, the need remains for innovative next generation vaccines that would incorporate protective Spike-derived B-cell epitopes that resist immune evasion. Towards that goal, in this study we (<i>i</i>) Screened the sequences of Spike among many VOCs and identified conserved and non-conserved linear B-cell epitopes; (<i>ii</i>) Compared titers and neutralization antibodies specific to these conserved and non-conserved B-cell epitopes from serum of symptomatic and asymptomatic COVID-19 patients that were exposed to multiple VOCs across the 5<sup>-</sup>year COVID-19 pandemic, and (<i>iii</i>) Compared protective efficacy of conserved versus non-conserved B-cell epitopes against the most pathogenic Delta variant in a \"humanized\" ACE-2/HLA transgenic mouse model. We found robust conserved B-cell epitope-specific antibody titers and neutralization in sera from asymptomatic COVID-19 patients. In contrast, sera from symptomatic patients contained weaker antibody responses specific to conserved B-cell epitopes. A multi-epitope COVID-19 vaccine that incorporated the conserved B-cell epitopes, but not the non-conserved B-cell epitopes, significantly protected the ACE2/HLA transgenic mice against infection and COVID-19 like symptoms caused by the Delta variant. These findings underscore the importance of conserved B-cell epitopes in generating robust protective immunity against severe COVID-19 symptoms caused by various VOCs, providing valuable insights for the development of broad-spectrum next generation Coronavirus vaccines capable of conferring cross-variant protective immunity."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.09.22.614369"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11463540"],"repository":["biostudies-literature"],"pubmed_title":["Dynamics of Spike-Specific Neutralizing Antibodies Across Five-Year Emerging SARS-CoV-2 Variants of Concern Reveal Conserved Epitopes that Protect Against Severe COVID-19."],"pmcid":["PMC11463540"],"funding_grant_id":["R01 AI158060","R21 AI147499","R01 AI143348","R01 AI150091","R41 AI138764","R43 AI124911","R21 AI110902","R21 AI143326","R43 AI174383"],"pubmed_authors":["Zayou L","Lemkhente Z","Vahed H","Quadiri A","Prakash S","Dhanushkodi NR","Gil D","BenMohamed L","Ulmer JB","Belmouden A","Chentoufi A"],"additional_accession":[]},"is_claimable":false,"name":"Dynamics of Spike-Specific Neutralizing Antibodies Across Five-Year Emerging SARS-CoV-2 Variants of Concern Reveal Conserved Epitopes that Protect Against Severe COVID-19.","description":"Since early 2020, several SARS-CoV-2 variants of concern (VOCs) continue to emerge, evading waning antibody mediated immunity produced by the current Spike-alone based COVID-19 vaccines. This caused a prolonged and persistent COVID-19 pandemic that is going to enter its fifth year. Thus, the need remains for innovative next generation vaccines that would incorporate protective Spike-derived B-cell epitopes that resist immune evasion. Towards that goal, in this study we (<i>i</i>) Screened the sequences of Spike among many VOCs and identified conserved and non-conserved linear B-cell epitopes; (<i>ii</i>) Compared titers and neutralization antibodies specific to these conserved and non-conserved B-cell epitopes from serum of symptomatic and asymptomatic COVID-19 patients that were exposed to multiple VOCs across the 5<sup>-</sup>year COVID-19 pandemic, and (<i>iii</i>) Compared protective efficacy of conserved versus non-conserved B-cell epitopes against the most pathogenic Delta variant in a \"humanized\" ACE-2/HLA transgenic mouse model. We found robust conserved B-cell epitope-specific antibody titers and neutralization in sera from asymptomatic COVID-19 patients. In contrast, sera from symptomatic patients contained weaker antibody responses specific to conserved B-cell epitopes. A multi-epitope COVID-19 vaccine that incorporated the conserved B-cell epitopes, but not the non-conserved B-cell epitopes, significantly protected the ACE2/HLA transgenic mice against infection and COVID-19 like symptoms caused by the Delta variant. These findings underscore the importance of conserved B-cell epitopes in generating robust protective immunity against severe COVID-19 symptoms caused by various VOCs, providing valuable insights for the development of broad-spectrum next generation Coronavirus vaccines capable of conferring cross-variant protective immunity.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-04-08T18:41:30.146Z","creation":"2025-04-06T01:58:06.597Z"},"accession":"S-EPMC11463540","cross_references":{"pubmed":["39386567"],"doi":["10.1101/2024.09.22.614369"]}}