Altered baseline immunological state and impaired immune response to SARS-CoV-2 mRNA vaccination in lung transplant recipients.

Summary

Using systems immunology, the study shows that lung transplant recipients have a baseline immune state akin to sepsis and severe COVID-19 (high EN-RAGE/IL-6, low HLA-DR), and mount blunted antibody, B-cell, T-cell, and innate responses to mRNA vaccination. Single-cell and plasma analyses link these baseline features to impaired vaccine responsiveness.

Key Findings

• Baseline immune profile in lung transplant recipients mirrors severe COVID-19/sepsis: high EN-RAGE (S100A12) and IL-6, reduced HLA-DR on monocytes/dendritic cells, impaired cytokine production, and elevated plasma microbial products.
• Single-cell RNA-seq reveals an expanded monocyte cluster with high S100A family expression and reduced cytokine/antigen presentation gene expression.
• Post-vaccination, antibody, B-cell, T-cell, and innate immune signatures are diminished compared to healthy controls.
• Integrative analysis links baseline immune dysregulation to impaired vaccine responses.

Clinical Implications

Suggests individualized vaccine schedules, adjuncts (e.g., adjuvants), and immune monitoring (e.g., HLA-DR, EN-RAGE) in lung transplant recipients; informs risk assessment for infections including sepsis-like complications.

Limitations

• Sample size and center-level details are not specified in the abstract, limiting assessment of generalizability.
• Observational design precludes causal inference; immunosuppressive regimens may confound associations.

Future Directions

Test immunomodulatory or adjuvant strategies to enhance vaccine responses; validate biomarkers (HLA-DR, EN-RAGE/S100A12) for risk stratification across transplant centers.