Functional CVIDs phenotype clusters identified by the integration of immune parameters after BNT162b2 boosters

Area of Science:

• Immunology
• Vaccinology
• Medical Diagnostics

Background:

• Assessing vaccine response is a diagnostic criterion for Common Variable Immune Deficiencies (CVIDs).
• SARS-CoV-2 vaccination provided a novel antigen to study immune responses in CVIDs patients.
• Understanding immune memory in CVIDs is critical for patient management.

Purpose of the Study:

• To analyze the immune response to SARS-CoV-2 vaccination in CVIDs patients.
• To identify distinct CVIDs patient phenotypes based on immune parameters after BNT162b2 boosters.
• To evaluate the utility of different immunological readouts for assessing vaccine efficacy in CVIDs.

Main Methods:

• Longitudinal study of 47 CVIDs patients receiving 3rd and 4th BNT162b2 vaccine doses.
• Measurement of specific and neutralizing antibodies, spike-specific memory B cells, and functional T cells.
• Integration of immune parameters to identify patient clusters.

Main Results:

• Vaccine response varied significantly depending on the efficacy readout used.
• While 63.8% of patients had detectable serum antibodies, only 30% exhibited high-affinity memory B cells and recall responses.
• Four distinct CVIDs patient clusters were identified based on B cell phenotypes and T cell functions.

Conclusions:

• Antibody presence alone is insufficient to confirm established immune memory in CVIDs.
• In-vivo vaccination response measurements effectively distinguish CVIDs patients with different immunological defects and clinical outcomes.
• Phenotypic clustering aids in understanding the heterogeneity of immune responses in CVIDs.