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

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 12; p. 1918
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.06.2022; MDPI
• Subjects: Antibodies; Antibodies, Viral; Autoimmune diseases; Autoimmunity; BNT162 Vaccine; BNT162b2; CD4 antigen; CD40 Ligand; CD40L protein; CD45 antigen; CD8 antigen; Common Variable Immune Deficiencies; Coronaviruses; COVID-19; COVID-19 - prevention & control; Genes; Humans; Immune system; Immunization; Immunoglobulin A; Immunoglobulin G; Immunological memory; Immunology; Infections; Lung diseases; Lymphocytes; Lymphocytes T; Memory cells; mRNA; mRNA Vaccines; Patients; Peripheral blood; Phenotypes; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike protein; T-cells; Tumor Necrosis Factor-alpha; Tumor necrosis factor-α; vaccine; Vaccines; Vaccines, Synthetic; Variables; γ-Interferon; United States > US; Germany; COVID-19; T-cells; SARS-CoV-2; vaccine; BNT162b2; antibody response; booster dose; spike protein; Common Variable Immune Deficiencies; memory B cells
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11121918

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.