Frontiers in Immunology (May 2023)

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

  • Eva Piano Mortari,
  • Eva Piano Mortari,
  • Federica Pulvirenti,
  • Valentina Marcellini,
  • Sara Terreri,
  • Ane Fernandez Salinas,
  • Simona Ferrari,
  • Giulia Di Napoli,
  • Daniele Guadagnolo,
  • Eleonora Sculco,
  • Christian Albano,
  • Marika Guercio,
  • Stefano Di Cecca,
  • Cinzia Milito,
  • Giulia Garzi,
  • Anna Maria Pesce,
  • Livia Bonanni,
  • Matilde Sinibaldi,
  • Veronica Bordoni,
  • Serena Di Cecilia,
  • Silvia Accordini,
  • Concetta Castilletti,
  • Chiara Agrati,
  • Concetta Quintarelli,
  • Salvatore Zaffina,
  • Franco Locatelli,
  • Franco Locatelli,
  • Rita Carsetti,
  • Isabella Quinti

DOI
https://doi.org/10.3389/fimmu.2023.1194225
Journal volume & issue
Vol. 14

Abstract

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IntroductionAssessing the response to vaccinations is one of the diagnostic criteria for Common Variable Immune Deficiencies (CVIDs). Vaccination against SARS-CoV-2 offered the unique opportunity to analyze the immune response to a novel antigen. We identify four CVIDs phenotype clusters by the integration of immune parameters after BTN162b2 boosters.MethodsWe performed a longitudinal study on 47 CVIDs patients who received the 3rd and 4th vaccine dose of the BNT162b2 vaccine measuring the generation of immunological memory. We analyzed specific and neutralizing antibodies, spike-specific memory B cells, and functional T cells.ResultsWe found that, depending on the readout of vaccine efficacy, the frequency of responders changes. Although 63.8% of the patients have specific antibodies in the serum, only 30% have high-affinity specific memory B cells and generate recall responses.DiscussionThanks to the integration of our data, we identified four functional groups of CVIDs patients with different B cell phenotypes, T cell functions, and clinical diseases. The presence of antibodies alone is not sufficient to demonstrate the establishment of immune memory and the measurement of the in-vivo response to vaccination distinguishes patients with different immunological defects and clinical diseases.

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