tetano
Editor, Senior Moderator
Front Immunol
. 2025 Feb 18:16:1503954.
doi: 10.3389/fimmu.2025.1503954. eCollection 2025. 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
Latifa Zayou[SUP] #[/SUP][SUP] 1 2 [/SUP], Swayam Prakash[SUP] #[/SUP][SUP] 1 [/SUP], Hawa Vahed[SUP] 3 [/SUP], Nisha Rajeswari Dhanushkodi[SUP] #[/SUP][SUP] 1 [/SUP], Afshana Quadiri[SUP] #[/SUP][SUP] 1 [/SUP], Ahmed Belmouden[SUP] 2 [/SUP], Zohra Lemkhente[SUP] 4 [/SUP], Aziz Chentoufi[SUP] 1 [/SUP], Daniel Gil[SUP] 3 [/SUP], Jeffrey B Ulmer[SUP] 3 [/SUP], Lbachir BenMohamed[SUP] 1 3 5 6 [/SUP]
Affiliations
Introduction: 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.
Methods: Towards that goal, in this study we (i) Screened the sequences of Spike among many VOCs and identified conserved and non-conserved linear B-cell epitopes; (ii) 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-year COVID-19 pandemic, and (iii) 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.
Results: 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.
Discussion: 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.
Keywords: B cell epitopes; COVID-19; SARS-CoV-2; age; antibodies; disease severity. cross-protective conserved B cell epitopes; gender.
. 2025 Feb 18:16:1503954.
doi: 10.3389/fimmu.2025.1503954. eCollection 2025. 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
Latifa Zayou[SUP] #[/SUP][SUP] 1 2 [/SUP], Swayam Prakash[SUP] #[/SUP][SUP] 1 [/SUP], Hawa Vahed[SUP] 3 [/SUP], Nisha Rajeswari Dhanushkodi[SUP] #[/SUP][SUP] 1 [/SUP], Afshana Quadiri[SUP] #[/SUP][SUP] 1 [/SUP], Ahmed Belmouden[SUP] 2 [/SUP], Zohra Lemkhente[SUP] 4 [/SUP], Aziz Chentoufi[SUP] 1 [/SUP], Daniel Gil[SUP] 3 [/SUP], Jeffrey B Ulmer[SUP] 3 [/SUP], Lbachir BenMohamed[SUP] 1 3 5 6 [/SUP]
Affiliations
- PMID: 40040708
- PMCID: PMC11876060
- DOI: 10.3389/fimmu.2025.1503954
Introduction: 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.
Methods: Towards that goal, in this study we (i) Screened the sequences of Spike among many VOCs and identified conserved and non-conserved linear B-cell epitopes; (ii) 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-year COVID-19 pandemic, and (iii) 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.
Results: 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.
Discussion: 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.
Keywords: B cell epitopes; COVID-19; SARS-CoV-2; age; antibodies; disease severity. cross-protective conserved B cell epitopes; gender.