Spike Glycoprotein Epitopes | ||||
| Region | Conservation | Function | Immune Response | References |
| S2 subunit (Fusion Peptide, FP) | Highly conserved across all betacoronaviruses | Critical for virus-cell membrane fusion | Antibodies block membrane fusion and viral entry | |
| S2 subunit (Fusion Loop) | 63%–98% conservation across human coronaviruses. Highly conserved acrossSARS-CoV-2 variants | Critical for virus-cell membrane fusion | Antibodies block membrane fusion and viral entry | Schendel 2025 |
| S2 subunit (Heptad Repeat 1, HR1) | Moderately conserved across betacoronaviruses | Essential for forming the six-helix bundle needed for membrane fusion | Antibodies inhibit six-helix bundle formation | |
| S2 subunit (Stem Helix) | Highly conserved across all coronaviruses | Stabilizes fusion machinery and supports membrane fusion | Antibodies prevent viral fusion and entry | |
| S2 subunit (Upstream Helix) | Highly conserved across SARS-CoV-2 variants, moderately conserved across betacoronaviruses | Important for spike protein structural stability | Antibodies block conformational changes, locking the spike protein in the pre-fusion conformation | Liu 2025 |
| S2 subunit (Fusion Peptide Proximal Region, FPPR) | Conserved across betacoronaviruses | Adjacent to FP, supports spike conformational changes | Antibodies prevent fusion; strong synergy with FP-targeting antibodies | |
| S1 subunit (N-terminal domain, NTD) | Conserved across SARS-CoV-2 variants | Contributes to viral entry and immune evasion | Antibodies block viral entry and enhance Fc-mediated effector functions | |
| S1 subunit (Subdomain 1, SBD) | Conserved across SARS-CoV-2 variants | Stabilizes spike protein in prefusion state | Antibodies reduce spike conformational flexibility | Magazine 2024 |
| S1-S2 boundary region | Conserved across SARS-CoV-2 variants | Regulates spike cleavage and activation | Generates strong IgG response | Zayou 2025 |
| S1 subunit upstream of the furin cleavage site | Conserved across sarbecoviruses | May regulate spike cleavage | Strong IgG response generation | Diaz 2025 |
| S2 subunit downstream of the furin cleavage site | Conserved across sarbecoviruses | Unknown post-cleavage function | Generates broadly protective IgG response | Diaz 2025 |
| S2 subunit (Hinge Region, connecting HR1 & central helix) | Conserved across betacoronaviruses | Allows spike flexibility and fusion | Antibodies blocks viral entry via Fc-mediated response | Silva 2023 |
| S2 subunit (Engineered Stabilized Stem) | Created as a stabilized construct for vaccination | Enhances immune recognition while preventing excessive conformational change | Provides potent neutralization across multiple sarbecoviruses | Hsieh 2024 |
| RBD-8 (Cryptic RBD Epitope) | Cryptic, conserved (across sarbecoviruses), non-RBM epitope on the RBD, centered on residues W353, R355, R357, D428, K462–I468, E516, and L518. | Antibodies targeting RBD-8 interfere with conformational changes, indirectly impairing ACE2 engagement. | Antibodies prevent ACE2 binding, blocking viral entry. | Feng 2025 |
T-cell epitopes | ||||
| Epitope | Protein | Conservation | Immune Features | Source |
| N262–270 | N | Conserved between SARS-CoV-2 and SARS-CoV (K→Q at position 266) | Retains structural similarity; allows cross-reactivity | Wang 2024 |
| N266–274 | N | Conserved between SARS-CoV-2 and SARS-CoV (A→Q at position 267) | High conservation of binding regions; presented by multiple HLA alleles → broad coverage | Wang 2024 |
| N261–277 | N | Minor variations between SARS-CoV and SARS-CoV-2 | Retains cross-reactivity; stimulates CD4+ and CD8+ T cells; recognized across diverse HLA types | Wang 2024 |
| M105–113 | M | Conserved across SARS-CoV-2 VOCs | CD8+ T cell epitope | Meyer 2023 |
| ORF3a(206–215) | ORF3a | Conserved across SARS-CoV-2 VOCs | CD8+ T cell epitope | Meyer 2023 |
| ORF3a(203–212) | ORF3a | Conserved across SARS-CoV-2 VOCs | CD8+ T cell epitope | Meyer 2023 |
| ORF3a(139–147) | ORF3a | Conserved across SARS-CoV-2 VOCs | CD8+ T cell epitope | Meyer 2023 |