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
Federica Pulvirenti,
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,
Isabella Quinti
Affiliations
Federica Pulvirenti
Reference Centre for Primary Immune Deficiencies, Azienda Ospedaliera Universitaria Policlinico Umberto I, 00185 Rome, Italy
Stefano Di Cecca
Department Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, 00116 Rome, Italy
Matilde Sinibaldi
Department Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, 00116 Rome, Italy
Eva Piano Mortari
B Cell Unit, Immunology Research Area, Bambino Gesù Children’s Hospital, IRCCS, Viale di San Paolo, 00146 Rome, Italy
Sara Terreri
B Cell Unit, Immunology Research Area, Bambino Gesù Children’s Hospital, IRCCS, Viale di San Paolo, 00146 Rome, Italy
Christian Albano
B Cell Unit, Immunology Research Area, Bambino Gesù Children’s Hospital, IRCCS, Viale di San Paolo, 00146 Rome, Italy
Marika Guercio
Department Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, 00116 Rome, Italy
Eleonora Sculco
Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy
Cinzia Milito
Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy
Simona Ferrari
Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
Franco Locatelli
Department Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, 00116 Rome, Italy
Concetta Quintarelli
Department Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, 00116 Rome, Italy
Rita Carsetti
B Cell Unit, Immunology Research Area, Bambino Gesù Children’s Hospital, IRCCS, Viale di San Paolo, 00146 Rome, Italy
Isabella Quinti
Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy
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.
