scholarly journals HUMORAL AND CELLULAR IMMUNOGENICITY and SAFETY UP TO 4 MONTHS AFTER VACCINATION WITH BNT162B2 mRNA COVID-19 VACCINE IN HEART AND LUNG TRANSPLANTED YOUNG ADULTS

2021 ◽  
Author(s):  
Nicola Cotugno ◽  
Chiara Pighi ◽  
Elena Morrocchi ◽  
Alessandra Ruggiero ◽  
Donato Amodio ◽  
...  
Keyword(s):  
T Cells ◽  
Young Adults ◽  
Cd4 T Cells ◽  
Organ Transplant ◽  
Solid Organ ◽  
Close Monitoring ◽  
Transplant Recipients ◽  
Short Term ◽  
Solid Organ Transplant Recipients

Background: Immunizations among vulnerable population, including solid organ transplant recipients (SOT), present suboptimal responses at vaccination and over time. We investigated safety and immunogenicity of the BNT162B2 mRNA COVID-19 vaccine in 34 SOT young adults as compared to 36 healthy controls (HC). Methods: immunogenicity was measured through the analysis of anti SARS-CoV2 IgG Antibodies and antigen specific CD4 T cells (CD40L+), detected by flow cytometry before vaccination, 21 days after priming (T21), 7 days after booster dose (T28) and 2-4 months after priming (T120). Baseline T and B cell immune phenotype was deeply investigated. The safety profile was investigated by close monitoring and self-reported diary. Results: Anti-S and anti-Trimeric Ab responses were significantly lower in SOT vs HC at T21 (p<0.0001) and at T28 (p<0.0001). Ten out of 34 SOT (29%) at T28 and 3 out of 33 (9%) at T120 had undetectable SARS-CoV-2 IgG. The analysis of SARS-CoV-2 specific CD4 T cells showed lower CD40L expression after in vitro stimulation in SOT compared to HC. Lower frequencies of memory B cells were found in patients not responding to vaccination. Lack of seroconversion was higher in patients treated with mycophenolate (p=0.0005). The vaccination was safe and well tolerated. Only short-term adverse events, were reported and no hospitalization or graft rejection were observed after vaccinations. Conclusions: These data show that SOT have a suboptimal immune response following mRNA vaccinations as compared to HC. Alternative strategies should be investigated to improve the immunization against SARS-CoV-2 in these patients.

scholarly journals Age-Dependent Association between Low Frequency of CD27/CD28 Expression on pp65 CD8+ T Cells and Cytomegalovirus Replication after Transplantation

2009 ◽  
Vol 16 (10) ◽  
pp. 1429-1438 ◽  
Author(s):  
Sara Cantisán ◽  
Julián Torre-Cisneros ◽  
Rosario Lara ◽  
Alberto Rodríguez-Benot ◽  
Francisco Santos ◽  
...  
Keyword(s):  
T Cells ◽  
Organ Transplant ◽  
Low Frequency ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cross Sectional ◽  
Organ Transplant Recipients ◽  
Hcmv Replication ◽  
Solid Organ Transplant Recipients

ABSTRACT In this cross-sectional study of 42 solid organ transplant recipients, the association of human cytomegalovirus (HCMV) replication and age with the phenotype of the HCMV-specific CD8+ T cells was analyzed by using the CMV pp65 HLA-A*0201 pentamer. A correlation between the proportion of CD28− HCMV-specific CD8+ T cells and age was observed in patients without HCMV replication (r = 0.50; P = 0.02) but not in patients with HCMV replication (r = −0.05; P = 0.83), a finding which differs from that observed for total CD8+ T cells. Within the group of patients younger than 50 years of age, patients with HCVM replication after transplantation had higher percentages of CD28− HCMV-specific CD8+ T cells (85.6 compared with 58.7% for patients without HCMV replication; P = 0.004) and CD27− HCMV-specific CD8+ T cells (90.7 compared with 68.8% for patients without HCMV replication; P = 0.03). However, in patients older than age 50 years, a high frequency of these two subpopulations was observed in patients both with and without previous HCMV replication (for CD28− HCMV-specific CD8+ T cells, 84.4 and 80.9%, respectively [P = 0.39]; for CD27− HCMV-specific CD8+ T cells 86.6 and 81.5%, respectively [P = 0.16]). In conclusion, the present study shows that in the group of recipients younger than age 50 years, HCMV replication after transplantation is associated with a high percentage of CD27− and CD28− HCMV-specific CD8+ T cells. These results suggest that the increased percentage of CD27− or CD28− HCMV-specific subsets can be considered a biomarker of HCMV replication in solid organ transplant recipients younger than age 50 years but not in older patients. Further studies are necessary to define the significance of these changes in HCMV-associated clinical complications posttransplantation.

scholarly journals Cellular immunity predominates over humoral immunity after the first dose of COVID-19 vaccines in solid organ transplant recipients

2021 ◽  
Author(s):  
Tina Schmidt ◽  
Verena Klemis ◽  
David Schub ◽  
Sophie Schneitler ◽  
Matthias Christian Reichert ◽  
...  
Keyword(s):  
T Cells ◽  
Humoral Immunity ◽  
Cellular Immunity ◽  
Cd8 T Cells ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Specific Antibodies ◽  
Solid Organ Transplant Recipients

Knowledge on the vaccine-induced cellular and humoral immunity and on immunogenicity of vector-based and mRNA vaccines in solid organ transplant recipients is limited. Therefore, SARS-CoV-2 specific T-cells and antibodies were analyzed in 40 transplant recipients and 70 age-matched controls after the first dose of vector-based or mRNA vaccines. Plasmablasts and SARS-CoV-2 specific CD4 and CD8 T-cells were quantified using flow-cytometry. Specific antibodies were analyzed by ELISA and neutralization assay. SARS-CoV-2 specific antibodies and T-cells were induced in both groups with significantly lower levels in patients. While antibodies were detected in 80% of controls and 5.3% of patients, specific CD4 and/or CD8 T-cells were more frequently found in both controls (84.3%) and patients (23.7%). The two vaccine types showed notable differences, as IgG and neutralizing activity were more pronounced after mRNA vaccination (p<0.0001 each), whereas CD4 and CD8 T-cell levels were higher after vector vaccination (p=0.009; p<0.0001). Plasmablast numbers were significantly higher in controls and correlated with SARS-CoV-2 specific IgG- and CD4 T-cell levels. In conclusion, assessment of antibodies is not sufficient to identify COVID-19-vaccine responders. Together with differences in immunogenicity among vaccines, this necessitates combined analysis of humoral and cellular immunity to reliably assess responders among immunocompetent and immunocompromised individuals.

Considerations for Using Ketoconazole in Solid Organ Transplant Recipients Receiving Cyclosporine Immunosuppression

1996 ◽  
Vol 6 (3) ◽  
pp. 148-154
Author(s):  
Scott A Chapman ◽  
Kathleen D Lake ◽  
Diane F Solbrack ◽  
Sherry K Milfred ◽  
Peter S Marshall ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Organ Transplant ◽  
Cost Savings ◽  
Solid Organ ◽  
Close Monitoring ◽  
Transplant Recipients ◽  
Potential Cost ◽  
Patients At Risk ◽  
Solid Organ Transplant Recipients ◽  
Cytochrome P 450

Drug interactions involving cyclosporine following transplantation are a challenging issue for the transplant clinician. This is especially true when ketoconazole is the second agent used in conjunction with cyclosporine. Because both agents are metabolized by the cytochrome P-450 IIIA4 enzyme system, cyclosporine levels rise dramatically in the presence of ketoconazole. Many other agents interact with ketoconazole, either by competitive enzyme inhibition in the liver and gastrointestinal tract, or by reducing the absorption of ketoconazole by agents that increase the pH of the gastrointestinal tract. Despite the potential cost savings when using ketoconazole to reduce cyclosporine doses, adverse effects associated with ketoconazole put patients at risk when using this combination. Close monitoring of cyclosporine levels is imperative when adding ketoconazole to cyclosporine, and once the dosage adjustments are complete, the addition of a third drug that interacts with either cyclosporine or ketoconazole could result in an unexpected rejection episode or toxic cyclosporine side effect.

scholarly journals Calcineurin Inhibitor Agents Interact Synergistically with Antifungal Agents In Vitro against Cryptococcus neoformans Isolates: Correlation with Outcome in Solid Organ Transplant Recipients with Cryptococcosis

2007 ◽  
Vol 52 (2) ◽  
pp. 735-738 ◽  
Author(s):  
Dimitrios P. Kontoyiannis ◽  
Russell E. Lewis ◽  
Barbara D. Alexander ◽  
Olivier Lortholary ◽  
Françoise Dromer ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Antifungal Agents ◽  
Immunosuppressive Agents ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
Solid Organ Transplant Recipients

ABSTRACT Synergistic interactions were observed between CIs and antifungal agents against 53 (90%) of 59 Cryptococcus neoformans isolates from solid organ transplant recipients with cryptococcosis and may account for better outcomes in patients with cryptococcosis receiving these immunosuppressive agents.

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