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

Front Immunol. 2023 May 25:14:1194225. doi: 10.3389/fimmu.2023.1194225. eCollection 2023.

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.

Keywords: BNT162b2; COVID-19; CVIDs; SARS-CoV-2; antibodies; booster dose; mRNA vaccine; memory B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing
  • BNT162 Vaccine
  • COVID-19*
  • Common Variable Immunodeficiency*
  • Humans
  • Longitudinal Studies
  • Phenotype
  • SARS-CoV-2

Substances

  • BNT162 Vaccine
  • Antibodies, Neutralizing

Grants and funding

The study was supported by funding of the Italian Ministry of Health COVID2020-12371817 and by Grant ‘‘5 per mille, 2021’’. Part of this research was supported by the Italian Ministry of Health “Fondi Ricerca Corrente” L3P1, and by EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT) to IRCCS Sacro Cuore Don Calabria Hospital. We warmly thanks IRCCS Policlinico S. Matteo, Pavia, for providing viral strains to perform neutralization tests. The research leading to these results has received funding from the European Union - NextGenerationEU through the Italian Ministry of University and Research under PNRR - M4C2-I1.3 Project PE_00000019 “HEAL ITALIA” to Isabella Quinti CUP: B53C22004000006.The views and opinions expressed are those of the authors only and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them. This work is generated within the European Reference Network for Rare Immunological Disorders (ERN-RITA).