Hybrid immunity-based induction of durable pan-endemic-coronavirus immunity in the elderly.

Summary

Hybrid immunity (vaccination plus SARS-CoV-2 infection) induces high-frequency, functionally avid pan-endemic-coronavirus reactive T cells across age groups, unlike vaccination alone. These spike-independent T cell responses may offset waning antibodies and immune escape, supporting inclusion of pan-coronavirus T cell epitopes in future vaccines, especially for the elderly.

Key Findings

• Hybrid immunity generated high frequencies of pan-human endemic coronavirus (PHEC)-reactive T cells across all age groups.
• Functional TCR avidities were comparable across ages and higher than in vaccination-only individuals.
• Spike-excluding peptide pools elicited robust T-cell responses, suggesting protection beyond spike-targeted immunity.
• Findings argue for inclusion of pan-coronavirus T-cell epitopes in future vaccine designs.

Clinical Implications

While not immediately altering clinical care, the data support vaccine strategies that incorporate conserved, non-spike T cell epitopes to protect older adults despite waning antibodies.

Limitations

• Cross-sectional immunologic assessment without clinical outcome endpoints
• Sample size and cohort composition details are not specified in the abstract

Future Directions

Prospective studies linking pan-coronavirus T-cell metrics to clinical protection and trials testing vaccines enriched for conserved T-cell epitopes in older adults.