AUTHOR=Piano Mortari Eva , Pulvirenti Federica , Marcellini Valentina , Terreri Sara , Salinas Ane Fernandez , Ferrari Simona , Di Napoli Giulia , Guadagnolo Daniele , Sculco Eleonora , Albano Christian , Guercio Marika , Di Cecca Stefano , Milito Cinzia , Garzi Giulia , Pesce Anna Maria , Bonanni Livia , Sinibaldi Matilde , Bordoni Veronica , Di Cecilia Serena , Accordini Silvia , Castilletti Concetta , Agrati Chiara , Quintarelli Concetta , Zaffina Salvatore , Locatelli Franco , Carsetti Rita , Quinti Isabella TITLE=Functional CVIDs phenotype clusters identified by the integration of immune parameters after BNT162b2 boosters JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1194225 DOI=10.3389/fimmu.2023.1194225 ISSN=1664-3224 ABSTRACT=Introduction

Assessing 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.

Methods

We 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.

Results

We 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.

Discussion

Thanks 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.