Induction of Cytomegalovirus-Specific T Cell Responses in Healthy Volunteers and Allogeneic Stem Cell Recipients Using Vaccination With Messenger RNA–Transfected Dendritic Cells
نویسندگان
چکیده
BACKGROUND Infection with human cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ and hematopoietic stem cell transplant (HSCT) recipients. METHODS The present study explored the safety, feasibility, and immunogenicity of CMV pp65 messenger RNA-loaded autologous monocyte-derived dendritic cells (DC) as a cellular vaccine for active immunization in healthy volunteers and allogeneic HSCT recipients. Four CMV-seronegative healthy volunteers and three allogeneic HSCT recipients were included in the study. Four clinical-grade autologous monocyte-derived DC vaccines were prepared after a single leukapheresis procedure and administered intradermally at a weekly interval. RESULTS De novo induction of CMV-specific T-cell responses was detected in three of four healthy volunteers without serious adverse events. Of the HSCT recipients, none developed CMV disease and one of two patients displayed a remarkable threefold increase in CMV pp65-specific T cells on completion of the DC vaccination trial. CONCLUSION In conclusion, our DC vaccination strategy induced or expanded a CMV-specific cellular response in four of six efficacy-evaluable study subjects, providing a base for its further exploration in larger cohorts.
منابع مشابه
Evaluating the Effects of Cytomegalovirus Glycoprotein B on the Maturation and Function of Monocyte-derived dendritic cells
Background & Objectives: Interaction of cytomegalovirus glycoprotein B with toll-like receptors of dendritic cells leads to early signaling and innate immune responses. The aim of this study is to evaluate the effects of cytomegalovirus glycoprotein B on the maturation and function of monocyte-derived dendritic cells in treated groups in comparison with control groups. Materials & Methods: Bloo...
متن کاملHighly Efficient Transfection of Dendritic Cells Derived from Esophageal Squamous Cell Carcinoma Patient: Optimization with Green Fluorescent Protein and Validation with Tumor RNA as a Tool for Immuno-genetherapy
This study was conducted to optimize a highly efficient mRNA transfection into dendritic cells (DC) derived from esophageal squamous cell carcinoma (ESCC) patients. Applying an electroporation technique, in vitro synthesized Green Fluorescent Protein (GFP) mRNA was transfected as an indicator into the DCs derived from a healthy donor. Flow cytometry revealed 84.9% transfection efficiency for DC...
متن کاملProspective simultaneous quantification of human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in young recipients of allogeneic hematopoietic stem cell transplants.
We investigated immune reconstitution against human cytomegalovirus (HCMV) in 57 hematopoietic stem cell transplant (HSCT) recipients, aged 1 to 24 years, through a novel method combining T-cell stimulation by HCMV-infected autologous dendritic cells with simultaneous cytometric quantification of HCMV-specific, IFNgamma-producing CD4(+) and CD8(+) T cells. Lymphoproliferative response (LPR) to ...
متن کاملالقای سلولهای دندریتیک تولروژن موشی با تنظیم کاهشی ملکول کمک تحریکی CD40 با استفاده از وکتور لنتی ویروس
Induction of Tolerogenic Murine Dendritic Cells by Downregulating the Co-stimulatory Molecule of CD40 Using Lentivirus Vector Mahmoodzadeh A1, Pourfatollah AA1, Karimi MH2, Moazzeni SM1 1Dept. of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran 2Transplantation Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran. Correspond Aut...
متن کاملبررسی تأثیر سرم موش حامله بر روی سلولهای دندریتیک در القاء تحریک لنفوسیتهای T و تولید سیتوکینهای IL-10 و IFN-γ Dendritic Cells and Antigen Specific T Cell Responses: Effect of Pregnant Mouse Serum
Background & Aim: Tolerance to the semi-allogenic fetal graft by the maternal immune system is a medical enigma that has stimulated investigations for a half of century. Several hypotheses have been proposed to explain the tolerance of mother to the fetus. The successful pregnancy is proposed and proved by many scientists to be a Th2 dominant phenomenon. This hypothesis is proved in most as...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 99 شماره
صفحات -
تاریخ انتشار 2015