BNT162b2 Elicited an Efficient Cell-Mediated Response against SARS-CoV-2 in Kidney Transplant Recipients and Common Variable Immunodeficiency Patients

Abstract

SARS-CoV-2 vaccination is the standard of care for the prevention of COVID-19 disease. Although vaccination triggers both humoral and cellular immune response, COVID-19 vaccination efficacy is currently evaluated by measuring antibodies only, whereas adaptative cellular immunity is unexplored. Our aim is to test humoral and cell-mediated response after three doses of BNT162b vaccine in two cohorts of fragile patients: Common Variable Immunodeficiency (CVID) patients and Kidney Transplant Recipients (KTR) patients compared to healthy donors. We enrolled 10 healthy controls (HCs), 19 CVID patients and 17 KTR patients. HC BNT162b third dose had successfully mounted humoral immune response. A positive correlation between Anti-Spike Trimeric IgG concentration and neutralizing antibody titer was also observed. CVID and KTR groups showed a lower humoral immune response compared to HCs. IFN-γ release induced by epitopes of the Spike protein in stimulated CD4⁺ and CD8⁺ T cells was similar among vaccinated HC, CVID and KTR. Patients vaccinated and infected showed a more efficient humoral and cell-mediated response compared to only vaccinated patients. In conclusion, CVID and KTR patients had an efficient cell-mediated but not humoral response to SARS-CoV-2 vaccine, suggesting that the evaluation of T cell responses could be a more sensitive marker of immunization in these subjects.

Keywords: cell-mediated immunity; humoral immunity; immunodeficiency; mRNA vaccine.

Figure 1

(A) Anti-Spike Trimeric IgG serum concentrations and (B) Neutralization titers 16–25 days after the third vaccination in Common Variable Immunodeficiency (CVID) patients, Kidney Transplant Recipients (KTR) and healthy donors. Data are shown as the median (horizontal black line), the 25th and 75th percentiles (boxes) and the 5th and 95th percentiles (whiskers) of 14 CVID, 14 KTR patients and 10 controls. (C) Correlation between Anti-Spike Trimeric IgG and Neutralization titers was assessed by Spearman’s correlation analysis and reported as coefficient of correlation. p < 0.05 was considered statistically significant.

Figure 2

INF-γ plasma levels after exposure of lymphocytes to SARS-COV-2 Ag1 (A) and Ag2. (B) Peptides 16–25 days after the third vaccination and not infected in healthy controls, CVID and KTR. Data are shown as the median (horizontal black line), the 25th and 75th percentiles (boxes) and the 5th and 95th percentiles (whiskers) of 14 CVID, 14 KTR patients and 10 controls. (C) Correlations between two variables: INF-γ induced by Ag1 and INF-γ induced by Ag1, andINF-γ induced by Ag1 and Anti-Spike Trimeric IgG. (D) INF-γ induced by Ag2 and Anti-Spike Trimeric IgG. (E) Levels in study population were assessed by Spearman’s correlation analysis and reported as coefficient of correlation. p < 0.05 was considered statistically significant.

Figure 3

IL-6 (A,B), CXCL8 (C,D), TNF-α (E,F) and IL-10 (G,H) plasma levels after exposure of lymphocytes to SARS-COV-2 Ag1 (A,C,E,G) and Ag2 (B,D,F,H) peptides 16–25 days after the third vaccination in CVID, KTR and healthy controls. Data are shown as the median (horizontal black line), the 25th and 75th percentiles (boxes) and the 5th and 95th percentiles (whiskers) of 14 CVID, 14 KTR patients and 10 controls. p < 0.05 was considered statistically significant.

Figure 4

(A) Anti-Spike Trimeric IgG serum concentrations, INF-γ plasma levels after exposure of lymphocytes to SARS-COV-2 Ag1 (B) and Ag2 (C) peptides in infected and vaccinated CVID and in infected and vaccinated KTR patients with or without Anti-SARS-CoV-2 Nucleocapsid (N) IgG. Data are shown as the median (horizontal black line), the 25th and 75th percentiles (boxes) and the 5th and 95th percentiles (whiskers) of CVID andKTR patients. p < 0.05 was considered statistically significant.