Transplantation Infection

Influenza virus is a significant pathogen in pediatric solid organ transplant (SOT) recipients. However, these individuals respond poorly to standard-dose (SD) inactivated influenza vaccine (IIV). Recent studies have investigated two strategies to overcome poor immune responses in SOT recipients: (1) administration of high-dose (HD)-IIV compared to SD-IIV and (2) two doses of SD-IIV compared to one dose of SD-IIV in the same influenza season. One study compared HD-IIV vs. SD-IIV in adult SOT recipients and noted that HD-IIV was safe and more immunogenic; however, the median post-transplant period was 38 months. A phase I pediatric study comparing a single dose of HD-IIV vs. SD-IIV was safe with higher immunogenicity, but the study was limited by small sample size and median post-transplant vaccine administration was 26 months. In another phase II trial of adult SOT recipients, two doses of SD-IIV one month apart compared to one-dose of SD-IIV revealed modestly increased immunogenicity when given at a median of 18 months post-transplant. Therefore, these studies lack both evaluation in the early post-transplant period and substantive pediatric populations. Additionally, the administration of two-doses of HD-IIV in the same influenza season has not been evaluated in pediatric SOT recipients. Thus, the optimal immunization strategy for pediatric SOT recipients less than 24 months post-transplant is unknown. In addition, immunologic predictors and correlates of influenza vaccine immunogenicity in pediatric SOT recipients have not been well-defined. The central hypothesis of our proposal is that pediatric SOT recipients 1-23 months post-transplant who receive two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have similar safety but higher Hemagglutination Inhibition (HAI) geometric mean titers (GMTs) to influenza antigens compared to pediatric SOT recipients receiving two doses of SD-QIV.

Lung allograft recipients have a higher burden of influenza disease and greater associated morbidity and mortality compared with healthy controls. Induction and early maintenance immunosuppression is thought to impair immunogenicity to standard dose inactivated influenza vaccine. This early post-transplant period is when immunity is most desirable, since influenza disease during this time frame is associated with adverse consequences. Thus, strategies to reduce severe influenza disease in this highly susceptible population are critical. No trials in lung transplant recipients have evaluated two doses of HD-IIV within the same influenza season as a strategy to improve immunogenicity and durability of influenza prevention. Furthermore, no influenza vaccine trials have focused on enrollment of subjects at early post-transplant timepoints. Very few studies have been performed in solely lung allograft recipients. Immunosuppression intensity is highest in lung patients, thereby limiting comparisons to recipients of heart, liver, and kidney transplants. Therefore, studies to assess both HD-IIV and two-dose strategies in the same influenza season in post-lung transplant recipients are greatly needed. The central hypothesis of our proposal is that lung allograft recipients who are 1-35 months post-transplant and receiving two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have higher HAI geometric mean titers (GMT) to influenza antigens compared to those receiving two doses of SD-QIV. To test this hypothesis and address the above critical knowledge gaps, we propose to conduct a phase II, multi-center, randomized, double-blind, controlled immunogenicity and safety trial comparing the administration of two doses of HD-QIV to two doses of SD-QIV in lung allograft recipients 1-35 months post-transplant. The results of this clinical trial will address significant knowledge gaps regarding influenza vaccine strategies (e.g., one vs. two doses and HD-QIV vs. SD-QIV) and immune responses in lung transplant recipients and will guide vaccine recommendations during the post-transplant period.

* Herpesvirus infections may be severe in immunocompromised patients, with a high risk of complications and mortality. * Recipients of hematopoietic stem cell transplant (HSCT) or patients receiving high-intensity chemotherapy for hematological malignancies are the most vulnerable individuals. * Although the worldwide prevalence of herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV), antiviral prophylaxis in seropositive HSCT recipients has significantly reduced the rate of infection. * Acyclovir (ACV) is the first-choice drug for the prophylaxis or the therapy of that kind of infection. * Since the beginning, ACV has demonstrated to be characterized by a large interpatient variability, especially in children. * Therefore, therapeutic drug monitoring and pharmacokinetic studies may help in optimizing drug in children with malignancies.

This project will provide novel data using a large cohort of more than 3000 transplanted patients. Risk and protective factors for SARS-CoV-2 infection and COVID-19 disease severity will be identified. The proportion of patients who develop antibodies after infection will be revealed. In this way the presence of these antibodies can be evaluated as a test for prior infection. Our study additionally will demonstrate how long these antibodies remain present and whether they are protective against a new infection.

Molecular monitoring is conducted in blood cells, plasma samples, urine samples and/or tissue from patients after kidney transplantation. In the present study the investigators examine the hypothesis that noninvasive diagnostic molecular monitoring can improve the outcome after transplantation. Routine clinical and laboratory data from serum and urine are evaluated at baseline and after 0-1-2-3-4-12-16-52 weeks and 1-2-3-4-5-6-7-8-9-10 years after kidney transplantation. Mononuclear cells were obtained from the blood and transcripts of several diagnostic genes (including GATA3 (Trans-acting T-cell-specific transcription factor3), GATA4 (Trans-acting T-cell-specific transcription factor4), GAPDH (Glyceraldehyde 3-phosphate dehydrogenase), TRPC3 (Transient receptor potential cononical type3), TRPC6 (Transient receptor potential cononical type6), granzyme B, perforin, FOXP3 (Forkhead box P3), ISG15 (Interferon-stimulated gene 15), Mx1 (Interferon-induced GTP-binding protein), MMP3 (Matrix metalloproteinase-3), MMP9 (Matrix metalloproteinase-9), long-non-coding RNA, and others) are quantified using standard quantitative RT-PCR (Reverse transcription polymerase chain reaction) techniques. Proteomic analysis were performed in plasma and urine samples. Polymorphisms of selected genes are analyzed using standard techniques. Data are analyzed by descriptive statistics. Differences between groups were analyzed using Mann-Whitney test or Kruskal-Wallis-test and Dunn's multiple comparison post-test, as appropriate. Associations between variables are analyzed using regression analyses. Contingency tables are analyzed using Fisher's exact test.