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 Jun 14;11(12):1918. doi: 10.3390/cells11121918.

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • BNT162 Vaccine*
  • CD40 Ligand
  • COVID-19* / prevention & control
  • Humans
  • Immunization
  • Immunoglobulin A
  • Immunoglobulin G
  • SARS-CoV-2
  • Tumor Necrosis Factor-alpha
  • Vaccines, Synthetic
  • mRNA Vaccines

Substances

  • Antibodies, Viral
  • Immunoglobulin A
  • Immunoglobulin G
  • Tumor Necrosis Factor-alpha
  • Vaccines, Synthetic
  • mRNA Vaccines
  • CD40 Ligand
  • BNT162 Vaccine

Grants and funding

This research was funded by: Italian Ministry of Health RF2013-02358960 grant; Italian Ministry of Health COVID-2020-12371817 grant.