T-Cell Defects Associated to Lack of Spike-Specific Antibodies after BNT162b2 Full Immunization Followed by a Booster Dose in Patients with Common Variable Immune Deficiencies

Pulvirenti, Federica; Di Cecca, Stefano; Sinibaldi, Matilde; Piano Mortari, Eva; Terreri, Sara; Albano, Christian; Guercio, Marika; Sculco, Eleonora; Milito, Cinzia; Ferrari, Simona; Locatelli, Franco; Quintarelli, Concetta; Carsetti, Rita; Quinti, Isabella

doi:10.3390/cells11121918

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T-Cell Defects Associated to Lack of Spike-Specific Antibodies after BNT162b2 Full Immunization Followed by a Booster Dose in Patients with Common Variable Immune Deficiencies

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Reference Centre for Primary Immune Deficiencies, Azienda Ospedaliera Universitaria Policlinico Umberto I, 00185 Rome, Italy

Department Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, 00116 Rome, Italy

B Cell Unit, Immunology Research Area, Bambino Gesù Children’s Hospital, IRCCS, Viale di San Paolo, 00146 Rome, Italy

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Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy

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Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy

Author to whom correspondence should be addressed.

Academic Editor: Franco Pandolfi

Cells 2022, 11(12), 1918; https://doi.org/10.3390/cells11121918

Received: 10 May 2022 / Revised: 3 June 2022 / Accepted: 9 June 2022 / Published: 14 June 2022

(This article belongs to the Collection Cellular Immunology and COVID-19)

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Abstract

Following the third booster dose of the mRNA vaccine, Common Variable Immune Deficiencies (CVID) patients may not produce specific antibodies against the virus spike protein. The T-cell abnormalities associated with the absence of antibodies are still a matter of investigation. Spike-specific IgG and IgA, peripheral T cell subsets, CD40L and cytokine expression, and Spike-specific specific T-cells responses were evaluated in 47 CVID and 26 healthy donors after three doses of BNT162b2 vaccine. Testing was performed two weeks after the third vaccine dose. Thirty-six percent of the patients did not produce anti-SARS-CoV-2 IgG or IgA antibodies. Non responder patients had lower peripheral blood lymphocyte counts, circulating naïve and central memory T-cells, low CD40L expression on the CD4+CD45+RO+ and CD8+CD45+RO+ T-cells, high frequencies of TNFα and IFNγ expressing CD8+ T-cells, and defective release of IFNγ and TNFα following stimulation with Spike peptides. Non responders had a more complex disease phenotype, with higher frequencies of structural lung damage and autoimmunity, especially autoimmune cytopenia. Thirty-five percent of them developed a SARS-CoV-2 infection after immunization in comparison to twenty percent of CVID who responded to immunization with antibodies production. CVID-associated T cell abnormalities contributed to the absence of SARS-CoV-2 specific antibodies after full immunization. View Full-Text

Keywords: Common Variable Immune Deficiencies; T-cells; SARS-CoV-2; COVID-19; BNT162b2; vaccine; booster dose; memory B cells; spike protein; antibody response

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MDPI and ACS Style

Pulvirenti, F.; Di Cecca, S.; Sinibaldi, M.; Piano Mortari, E.; Terreri, S.; Albano, C.; Guercio, M.; Sculco, E.; Milito, C.; Ferrari, S.; Locatelli, F.; Quintarelli, C.; Carsetti, R.; Quinti, I. T-Cell Defects Associated to Lack of Spike-Specific Antibodies after BNT162b2 Full Immunization Followed by a Booster Dose in Patients with Common Variable Immune Deficiencies. Cells 2022, 11, 1918. https://doi.org/10.3390/cells11121918

AMA Style

Pulvirenti F, Di Cecca S, Sinibaldi M, Piano Mortari E, Terreri S, Albano C, Guercio M, Sculco E, Milito C, Ferrari S, Locatelli F, Quintarelli C, Carsetti R, Quinti I. T-Cell Defects Associated to Lack of Spike-Specific Antibodies after BNT162b2 Full Immunization Followed by a Booster Dose in Patients with Common Variable Immune Deficiencies. Cells. 2022; 11(12):1918. https://doi.org/10.3390/cells11121918

Chicago/Turabian Style

Pulvirenti, Federica, Stefano Di Cecca, Matilde Sinibaldi, Eva Piano Mortari, Sara Terreri, Christian Albano, Marika Guercio, Eleonora Sculco, Cinzia Milito, Simona Ferrari, Franco Locatelli, Concetta Quintarelli, Rita Carsetti, and Isabella Quinti. 2022. "T-Cell Defects Associated to Lack of Spike-Specific Antibodies after BNT162b2 Full Immunization Followed by a Booster Dose in Patients with Common Variable Immune Deficiencies" Cells 11, no. 12: 1918. https://doi.org/10.3390/cells11121918

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T-Cell Defects Associated to Lack of Spike-Specific Antibodies after BNT162b2 Full Immunization Followed by a Booster Dose in Patients with Common Variable Immune Deficiencies

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