The Cellular and Humoral Immune Response to SARS-CoV-2 Messenger RNA Vaccines Is Significantly Better in Liver Transplant Patients Compared with Kidney Transplant Patients

Abstract

Patients after organ transplantation have impaired immune response after vaccination against the SARS-CoV-2 virus. So far, published studies have reported quite different response rates to SARS-CoV-2 vaccination, ranging from 15-79% in liver and kidney transplant recipients. Up to one year after the first vaccine dose, we analyzed the humoral and cellular immune response of 21 liver transplant (LTX) patients after vaccination with mRNA vaccines compared with 28 kidney transplant (KTX) patients. We evaluated IgG against the SARS-CoV-2 spike protein as well as SARS-CoV-2 specific T cells using an ELISpot assay that detected IFN-γ- and/or IL-2-expressing T cells. We found a cellular and/or humoral immune response in 100% of the LTX patients compared with 68% of the KTX patients. Antibody titers against the spike protein of SARS-CoV-2 were significantly higher in the LTX group, and significantly more LTX patients had detectable specific IL-2-producing T cells. The immunosuppression applied in our LTX cohort was lower compared with the KTX cohort (14% triple therapy in LTX patients vs. 79% in KTX patients). One year after the first vaccination, breakthrough infections could be detected in 41% of all organ transplant patients. None of those patients suffered from a severe course of COVID-19 disease, indicating that a partial vaccination response seemed to offer protection to immunosuppressed patients. The better immune response of LTX patients after SARS-CoV-2 vaccination might be due to less intense immunosuppressive therapy compared with KTX patients.

Keywords: SARS-CoV-2; immune response; immunosuppression; transplantation; vaccination.

Figure 1

Study flow chart. Shown is the study design with the vaccination times and the measurement times of the humoral and cellular vaccination response. The number of patients examined at each time point (BW1–BW4) is indicated. It is also shown how many and in which period after the first vaccination study participants received further booster vaccinations. BW: blood withdrawal; mo: month; LTX: liver transplant patients; KTX: kidney transplant patients, HV: healthy volunteer; B: Biontech/Pfizer vaccine BNT162b2 (Comirnaty^®); M: Moderna vaccine mRNA-1273 (Spikevax^®); A: Astrazeneca vaccine AZD1222 (Vaxzevria^®).

Figure 2

SARS-CoV-2 antigen-specific cellular response after two doses of BNT162b2 vaccine. The cellular vaccination response was measured by IL-2 and/or IFN-γ producing cells in each of the study groups four weeks after the first vaccination (BW1), four weeks after the second vaccination (BW2), and six months after the first vaccination (BW3) and is indicated as percentage of only IL-2, only IFN-γ, or IL-2- and IFN-γ-producing T cells.

Figure 3

Waning of the cellular immune response in SOT patients between 4 weeks after the second vaccine dose (BW2) and 6 months following the first vaccine dose (BW3). For all solid organ transplant recipients, the stimulation index (SI) of IL-2-producing T cells (A) and antibody titers against the SARS-CoV-2 spike protein (AU/mL) (B) are indicated. The red lines represent the LTX patients, the grey lines the KTX patients.

Figure 4

SARS-CoV-2 antigen humoral response after two doses of BNT162b2 vaccine. The humoral vaccination response was measured by IgG antibodies against the RBD of the SARS-CoV-2 spike protein four weeks after the first vaccination (BW1), four weeks after the second vaccination (BW2), and six months after the first vaccination (BW3) in each study group. Vaccination response was divided into groups of titer <50 AU/mL (negative), 50–1000 AU/mL (low/moderate), and >1000 AU/mL (high) and indicated as percentages.