Impaired Cellular Immunity and Elevated Myeloid Derived Suppressor Cells in Kidney Transplant Recipients with Impaired Antibody Response to Covid-19 Vaccination

ABSTRACT

Purpose: To evaluate post-vaccination cellular and antibody (Ab) immunity after COVID-19 vaccination in single blood samples from 17 kidney transplant (KT) recipients who had received COVID-19 vaccination Methods: We measured frequencies of peripheral blood T- and B-cells which expressed the inflammatory marker CD154 after overnight stimulation with peptide mixtures representing the spike protein S, its S2 component which is conserved between SARS-CoV-2 and human coronaviruses, and the S1 component, which is specific to SARS-CoV-2 and also contains its receptor binding domain (RBD). Serum from each sample was assayed for anti-RBD and anti-S IgG Abs with ELISA. Optical density at 450nm (OD450) of 0.45 or greater implied presence of either Ab. Frequencies of monocytic and polymorphonuclear (PMN) myeloid-derived suppressor cell were also measured with flow cytometry. Result(s) Median age was 40 yrs (range 25 to 83), malefemale gender distribution was 78. All recipients received mRNA vaccination. Anti-S-IgG and anti-RBD-IgG were detected in 11 (Ab+) and were absent in four (Ab-). Compared with Ab+ KT recipients, those who were Ab- had lower frequencies of S2-reactive and S-reactive B-cells (p<0.05), CD4+ and CD8+ T-cells (Table 1, Fig 1). S1-reactive T-cell and B-cells were non-detectable. Frequencies of PMN-MDSC were numerically higher in Ab- compared with Ab+ KT recipients (Mean +/- SEM 38.9+/-8.1 vs 19.4+/-1.8, p-value 0.1, NS). Significant negative correlation was observed between PMN-MDSC frequencies and strength of anti-RBD IgG and anti-SPIKE IgG (Fig 1). Conclusion(s) COVID-19 vaccination results in spike antigen reactive T- and B-cells in KT recipients who develop Abs after vaccination. Failure of an Ab response is associated with impaired B-cell responses to the spike antigen and an increase in circulating polymorphonuclear myeloid derived suppressor cells. (Table Presented).