This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Epstein-Barr virus (EBV) specific T cells play a central role controlling the replication of EBV throughout life. This is evidenced by the greatly increased incidence of EBV-associated lymphoproliferative diseases in immunocompromised patients. In addition, restoration of EBV-specific T cell-mediated immunity via adoptive transfer of ex vivo expanded EBV-specific cytotoxic T cells in patients who have undergone allogeneic bone marrow transplantation has been shown to mediate regression of post-transplant lymphoproliferative disorder (PTLD) lesions. PTLD is a major cause of morbidity and mortality in patients who have received solid organ transplants. In this population of patients, the source of EBV-specific T cells for adoptive transfer is highly problematic. The natural history of PTLD in solid organ recipients suggests that elicitation of a memory T cell response against EBV or the augmentation of an existing response is likely to reduce the incidence of PTLD in this population. A robust multivalent response seems most likely to remain effective in the face of therapeutic immunosuppression. A safe and feasible approach to accomplish this goal is the use of a cellular vaccine consisting of autologous EBV-infected lymphoblastoid cell lines (LCLs). The natural history of EBV infection and the immunogenicity of LCL in vitro suggest that this cellular vaccine may be a potent stimulator of EBV-specific T cell responses in vivo. The proposed study will test the safety and efficacy of a vaccine preparation consisting of an autologous Epstein-Barr virus (EBV)-infected lymphoblastoid cell line (LCL) in patients who are being considered for solid organ transplant. The LCL and the EBV will be inactivated by photochemical treatment that consists of amotosalen HCl (S-59) and UVA light. Forty patients (20 EBV seropositive and 20 seronegative) will be vaccinated on two occasions, 1 month apart. The primary surrogate endpoint for efficacy will be cellular responses to EBV latency antigens by intracellular cytokine synthesis. Measurements of humoral responses to EBV antigens will be done in both EBV seronegative and seropositive patients. The durability of these during the time course of this study will be characterized. Primary infection among seronegative patients will be characterized. Adverse events associated with the proposed vaccination scheme will be described.
SPECIFIC AIMS - To assess the efficacy of a vaccine consisting of photochemically treated autologous EBV-infected lymphoblastoid cells in generating EBV-specific T cell and antibody responses in EBV seronegative patients or boosting the response in seropositive patients being considered for solid organ transplant. - To identify adverse events associated with such a vaccine - To assess the ability of the vaccine to protect from EBV primary infection in EBV seronegative patients during the time course of the study.
| Robert Braši?, James; Mari, Zoltan; Lerner, Alicja et al. (2018) Remission of Gilles de la Tourette Syndrome after Heat-Induced Dehydration. Int J Phys Med Rehabil 6: |
| Altman, Matthew C; Whalen, Elizabeth; Togias, Alkis et al. (2018) Allergen-induced activation of natural killer cells represents an early-life immune response in the development of allergic asthma. J Allergy Clin Immunol 142:1856-1866 |
| AIDS-defining Cancer Project Working Group of IeDEA, COHERE in EuroCoord (2018) Non-Hodgkin lymphoma risk in adults living with HIV across five continents. AIDS 32:2777-2786 |
| Juraschek, Stephen P; Miller 3rd, Edgar R; Appel, Lawrence J (2018) Orthostatic Hypotension and Symptoms in the AASK Trial. Am J Hypertens 31:665-671 |
| Elion, Richard A; Althoff, Keri N; Zhang, Jinbing et al. (2018) Recent Abacavir Use Increases Risk of Type 1 and Type 2 Myocardial Infarctions Among Adults With HIV. J Acquir Immune Defic Syndr 78:62-72 |
| Al-Sofiani, Mohammed E; Yanek, Lisa R; Faraday, Nauder et al. (2018) Diabetes and Platelet Response to Low-Dose Aspirin. J Clin Endocrinol Metab 103:4599-4608 |
| Grover, Surbhi; Desir, Fidel; Jing, Yuezhou et al. (2018) Reduced Cancer Survival Among Adults With HIV and AIDS-Defining Illnesses Despite No Difference in Cancer Stage at Diagnosis. J Acquir Immune Defic Syndr 79:421-429 |
| Grams, Morgan E; Sang, Yingying; Ballew, Shoshana H et al. (2018) Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate. Kidney Int 93:1442-1451 |
| Yanik, Elizabeth L; Hernández-Ramírez, Raúl U; Qin, Li et al. (2018) Brief Report: Cutaneous Melanoma Risk Among People With HIV in the United States and Canada. J Acquir Immune Defic Syndr 78:499-504 |
| Aboud, Katherine S; Barquero, Laura A; Cutting, Laurie E (2018) Prefrontal mediation of the reading network predicts intervention response in dyslexia. Cortex 101:96-106 |
Showing the most recent 10 out of 1014 publications
