ABSTRACT
Solid organ transplant recipients have an increased morbidity and mortality after SARS-CoV-2 infection. Immune responses after the third/fourth vaccination against SARS-CoV-2 are insufficiently studied in patients after kidney transplantation (KTX). We analyzed immune responses at a median of 4 months after the third/fourth vaccination in KTX patients and compared them to healthy controls. Cellular immunity was assessed using interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) ELISpot assays. Neutralizing antibody titers were assessed against SARS-CoV-2 D614G (wild type) and the variants alpha, delta and omicron by a cell culture-based neutralization assay. Humoral immunity was also determined by a competitive fluorescence assay, using 11 different variants of SARS-CoV-2. Antibody ratios were measured by ELISA. KTX patients showed significantly lower SARSCoV- 2-specific IFN-gamma responses after booster vaccination than healthy controls. However, the SARS-CoV-2 specific IL-2 responses were comparable to the T cell responses of healthy controls. Cell culture-based neutralizing antibody titers were 1.3-fold higher in healthy controls for D614G, alpha and delta and 7.8-fold higher for omicron (p < 0.01). Healthy controls had approximately 2-fold higher concentrations of potential neutralizing antibodies against all 11 variants than KTX patients. However, more than 60% of the KTX patients exhibited antibodies to variants of SARS-CoV-2. In conclusion, KTX patients should be partly protected against SARSCoV- 2, either by cross-reactive T cells, especially those producing IL-2, or by neutralizing antibodies to SARSCoV- 2 variants.