| Immune CoP | Features | References |
| Neutralizing antibody (nAb) titers | Bind to viral antigens and prevent infection Currently the most reliable and utilized predictor of vaccine efficacy across platforms Hybrid immunity enhances predictive value. COVE trial (mRNA-1273): 10-fold nAb increase was associated with 72% lower risk of symptomatic Omicron infection. Variant escape: Infection with variants can show reduced effectiveness of ancestral nAbs. COVE trial thresholds: 251 AU/mL → 50% VE (vaccine efficacy); 891 AU/mL → 74% VE | |
| Binding antibody (bAb) titers | Bind to viral antigens, but do not necessarily block infection Spike-specific IgG/IgA bAbs correlate with protection, especially in elderly and immunocompromised patients. Hybrid immunity enhances predictive value. COVE trial: Post-booster bAb levels were inversely associated with Omicron infection risk. COVE trial: 10-fold increase in bAbs was associated with 84% lower risk of symptomatic Omicron infection. | |
| T-cell responses | Antigen-specific CD4+/CD8+ T cells are associated with long-term protection from severe disease. IFNγ+ CD4+ T cells are particularly predictive of strong vaccine response. Robust T cell responses are linked to lower rates of hospitalization and mortality. T cells are more likely to recognize conserved epitopes, allowing cross-variant efficacy. Spike-specific T cell responses correlate with reduced disease severity in breakthrough cases. Nucleocapsid-specific CD4/CD8 T cells also show promise as potential CoPs. Early mucosal CD8+ T cell responses are associated with viral control. Hybrid immunity yields stronger/broader T cell responses. | |
| IgA | Neutralizes the virus at mucosal entry points, reducing viral load and transmission risk High nasal IgA titers are associated with prevention of infection. Nasal IgA titers inversely correlate with breakthrough infections. | |
| IL-6, IL-8, IL-1β, and IFN-γ | Enhance antiviral responses, particularly in the respiratory tract High IFN-γ, IL-1β, and IL-8 in the mucosa is associated with mild disease. | |
| Other potential CoPs | Mucosal Interferon-Stimulated Gene (ISG) expression correlates with viral control (e.g. OAS2, OAS3, IFIT1, ISG15, ISG20, IFITM1, USP18) Mucosal CXCL10 and CXCL11 levels correlate with viral control. Upregulated Phospholipid Scramblase 1 (PLSCR1; restriction factor) is linked to improved viral control and milder disease. Salivary vimentin can serve as a biomarker for mucosal immune activity against SARS-CoV-2. In controlled human studies, it has been found that 3'-deoxy-3',4'-didehydro-cytidine (ddhC) acts as an interferon-driven acute-phase biomarker, with levels positively correlated with symptom scores and nasal viral load in SARS-CoV-2 and influenza A participants. |