COVID‐19 is associated with increased morbidity and mortality in transplant recipients. There are no efficacy data available regarding these patients with any of the available SARS‐CoV‐2 vaccines. We analyzed the humoral response following full vaccination with the BNT162b2 (Pfizer‐BioNTech) in 136 kidney transplant recipients, and compared it to 25 controls. In order to exclude prior exposure to the virus, only participants with negative serology to SARS‐CoV‐2 nucleocapsid protein were included. All controls developed a positive response to spike protein, while only 51 of 136 transplant recipients (37.5%) had positive serology (p < .001). Mean IgG anti‐spike level was higher in the controls (31.05 [41.8] vs. 200.5 [65.1] AU/mL, study vs. control, respectively, p < .001). Variables associated with null humoral response were older age (odds ratio 1.66 [95% confidence interval 1.17–2.69]), high‐dose corticosteroids in the last 12 months (1.3 [1.09–1.86]), maintenance with triple immunosuppression (1.43 [1.06–2.15]), and regimen that includes mycophenolate (1.47 [1.26–2.27]). There was a similar rate of side effects between controls and recipients, and no correlation was found between the presence of symptoms and seroconversion. Our findings suggest that most kidney transplant recipients remain at high risk for COVID‐19 despite vaccination. Further studies regarding possible measures to increase recipient's response to vaccination are required.

Background and aims Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk for lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population. Methods LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records. Results Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p=0.013) and mostly female (68%, p=0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p<0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/mL vs. 200.5 AU/mL in controls, p<0.001). Predictors for negative response among LT recipients were older age, lower eGFR, and treatment with high dose steroids and MMF. No serious adverse events were reported in both groups. Conclusion LT recipients developed substantially lower immunological response to Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibodies response include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population. Lay summary Liver Transplant recipients had a substantially inferior immunity to the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive , average antibody levels were two times less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.

Differentiated cell types derived from human embryonic stem cells (hESCs) may serve in the future to treat various human diseases. A crucial step toward their successful clinical application is to examine the immune response that might be launched against them after transplantation. We used two experimental platforms to examine the in vivo leukocyte response toward hESCs. First, immunocompetent and immunodeficient mouse strains were used to identify T cells as the major component that causes xenorejection of hESCs. Second, mice that were conditioned to carry peripheral blood leukocytes from human origin were used to test the human leukocyte alloresponse toward undifferentiated and differentiated hESCs. Using this model, we have detected only a minute immune response toward undifferentiated as well as differentiated hESCs over the course of 1 month, although control adult grafts were repeatedly infiltrated with lymphocytes and destroyed. Our data show that the cells evade immune destruction due to a low immunostimulatory potential. Nevertheless, a human cytotoxic T lymphocyte clone that was specifically prepared to recognize two hESC lines could lyse the cells after major histocompatibility complex class I (MHC-I) induction. Although MHC-I levels in hESCs are sufficient for rejection by cytotoxic T cells, our data suggest that the immunostimulatory capacity of the cells is very low. Thus, immunosuppressive regimens for hESC-based therapeutics could be highly reduced compared with conventional organ transplantation because direct allorejection processes of hESCs and their derivatives are considerably weaker. STEM CELLS 2006;24:221-229

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