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oai:figshare.com:article/33920581 2026-09-18T05:39:11Z category_696 portal_316 item_type_3 month_year_09_2026

Table 1_AI-guided epitope engineering of a SARS-CoV-2 spike antigen for broad sarbecovirus neutralization.docx Alexandru Odainic (12225710) Ioannis Vardaxis (17012379) Matheus Ferraz (23143355) Katrin E Wiese (25070230) Lisette A H M Cornelissen (25070233) Akhilesh Sharma (8800444) Richard Stratford (6708653) Trevor Clancy (235169) Kaïdre Bendjama (10034978) Genetic Immunology artificial intelligence broadly protective coronavirus immunoinformatics vaccine <p>The rapid evolution of SARS-CoV-2 and the ongoing risk of zoonotic spillover highlight the need for vaccines that provide broad protection beyond strain-specific immunity. Here, we present a structure-guided, AI-enabled strategy for rational antigen design that enhances cross-reactive B-cell epitope recognition across betacoronaviruses. By integrating comparative sequence analysis with conformational epitope prediction, we identified conserved epitope hotspots within the Spike receptor-binding domain and introduced targeted motif-level substitutions into a SARS-CoV-2 BA.2 backbone. Engineered Spike immunogens, delivered as mRNA-lipid nanoparticle vaccines, elicited robust antibody responses in mice and demonstrated broad neutralizing activity against antigenically diverse SARS-CoV-2 variants, including BA.5 and XBB.1.5, as well as zoonotic sarbecoviruses. Selected designs reached neutralisation breadth comparable to an Omicron-adapted clinical benchmark for shared SARS-CoV-2 antigens, while extending neutralising activity to divergent zoonotic sarbecoviruses. These findings show that minimal, structure-guided epitope remodeling can enhance the presentation of conserved epitopes and improve antibody breadth, providing a generalizable framework for designing vaccines resilient to viral evolution and future pandemic threats.</p> 2026-09-18T05:39:11Z Dataset Dataset 10.3389/fimmu.2026.1919664.s001 https://figshare.com/articles/dataset/Table_1_AI-guided_epitope_engineering_of_a_SARS-CoV-2_spike_antigen_for_broad_sarbecovirus_neutralization_docx/33920581 CC BY 4.0