B and T Cell Responses to SARS-CoV-2 Vaccination in Kidney and Liver Transplant Recipients with and without Previous COVID-19

Abstract

(1) Background: Vulnerable populations including transplant recipients are jeopardised by COVID-19. Herein, we report on B and T cell responses among liver and kidney organ recipients at our centre. (2) Methods: 23 liver and 45 kidney (14 thereof combined kidney/pancreas) transplanted patients were vaccinated with two doses of BNT162b2 followed by a booster dose of mRNA-1273 in 28 non-responders 4 months thereafter. Anti-SARS-CoV-2-Ig was measured by specific ELISA and virus neutralisation assay; T cell responses were measured by a spike protein-specific IFN-γ release assay. (3) Results: Compared to controls, B and T cell responses were weak in transplant recipients, particularly in those without prior exposure to SARS-CoV-2. Within this group, only 15% after the first and 58.3% after the second vaccination achieved seroconversion. A total of 14 out of 28 vaccination non-responders achieved a seroconversion after a third dose. Vaccination side effects were more frequent in healthy controls. The use of mycophenolate was associated with reduced anti-SARS-CoV-2-Ig production. (4) Conclusions: Our data confirm that vaccination responses are insufficient after standard vaccination in liver and kidney transplant recipients and are affected to a variable degree by specific immunosuppressants, particularly mycophenolate. Monitoring vaccination success and re-vaccinating those who are unresponsive seems prudent to achieve sufficient titres. Overall, prospective large-scale, multinational, multicentre studies or high-quality meta-analyses will be needed to generate personalised vaccination strategies in order to achieve protective immunity in high-risk, hard-to-immunize populations.

Keywords: COVID-19; SARS-CoV-2; T cell response; antibody response; kidney transplantation; liver transplantation; vaccination.

Figure 1

Vaccination with BNT162b2 results in reduced humoral and cellular responses in SOT recipients. (a) Anti-SARS-CoV-2 IgG titres (RU/mL) in healthy controls, LTX, and NTX + PTX recipients. Each triplet represents data within the indicated timepoints before and after vaccination. Participants with a positive history of COVID-19 prior to vaccination (pre-vac seropositive) are indicated in red. Values below the assay’s threshold of 8 RU/mL were set at 0.1 RU/mL. Data were log2 transformed. (b) Functional testing of antibodies using spike-pseudotyped vesicular stomatitis viruses (ptVSV). Titres ≤ 1:4 were considered negative. Each triplet represents data from the indicated timepoints before and after vaccination. (c) SARS-CoV-2 spike protein-specific T cells were studied by interferon-γ release assay (IGRA) in the indicated groups after two vaccinations at day 49. (d) Anti-SARS-CoV-2-Ig after booster vaccination with mRNA-1273. Combined violin- and scatterplots of SARS-CoV-2 IgG titres in SOT recipients after the second vaccination and after the third booster vaccination. A total of 14 out of 28 SOT recipients achieved a seroconversion. (a,b) Box plots represent values as median (bold horizontal line), 75% confidence interval (box), and minimum and maximum values (whiskers). Dot clouds represent individual values, and the numbers are indicated. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001; paired data were analysed by Friedman test followed by Dunn’s multiple comparison. (c,d) Each violin plot represents the distribution of IFN-γ (pg/mL) for individual groups, with the dashed line indicating the median and the dotted lines representing 75% confidence intervals. Each data point represents one participant. Kruskal–Wallis ANOVA followed by Dunn’s multiple comparison test. (a–d) Crtl = healthy control; LTX = liver transplant recipients; NTX + PTX = kidney + kidney/pancreas recipients.

Figure 2

Mycophenolate use drives humoral non-response in SOT patients after SARS-CoV-2 vaccination. (a,b) Anti-SARS-CoV-2 IgG titres (RU/mL) in SOT recipients with or without CNI (A) or with or without MF (B) treatment. Each pair of bars represents data from the indicated timepoints. Highlighted and zoomed-out data illustrate anti-SARS-CoV-2-Ig concentrations in additional subsets of SOT recipients on day 49. Data were log2 transformed. Box plots represent values as median (bold horizontal line), 75% confidence interval (box), and minimum and maximum values (whiskers). Dot clouds represent individual values, and the total numbers are indicated. Values below the assay’s threshold of 8 RU/mL were set at 0.1 RU/mL. ** p < 0.01; *** p < 0.001; **** p < 0.0001; groups were compared using Mann–Whitney-U or Kruskal–Wallis-ANOVA followed by Dunn’s multiple comparison.