The Epstein-Barr Virus Lytic Protein BZLF1 as a Candidate Target Antigen for Vaccine Development.
The Epstein-Barr virus (EBV) is an oncogenic, γ-herpesvirus associated with a broad spectrum of disease. Although most immune-competent individuals can effectivley develop efficient adaptive immune responses to EBV, immunocompromised individuals are at serious risk for developing life-threatening diseases, such as Hodgkin lymphoma and posttransplant lymphoproliferative disorder (PTLD). Given the significant morbidity associated with EBV infection in high-risk populations, there is a need to develop vaccine strategies that restore or enhance EBV-specific immune responses. Here, we identify the EBV immediate-early protein BZLF1 as a potential target antigen for vaccine development. Primary tumors from patients with PTLD and a chimeric human-murine model of EBV-driven lymphoproliferative disorder (EBV-LPD) express BZLF1 protein. Pulsing human dendritic cells (DC) with recombinant BZLF1 followed by incubation with autologous mononuclear cells led to expansion of BZLF1-specific CD8(+) T cells in vitro and primed BZLF1-specific T-cell responses in vivo. In addition, vaccination of hu-PBL-SCID mice with BZLF1-transduced DCs induced specific cellular immunity and significantly prolonged survival from fatal EBV-LPD. These findings identify BZLF1 as a candidate target protein in the immunosurveillance of EBV and provide a rationale for considering BZLF1 in vaccine strategies to enhance primary and recall immune responses and potentially prevent EBV-associated diseases.
The Comprehensive Cancer Center and Arthur G. James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio.
Alex S
AS
Hartlage
The Comprehensive Cancer Center and Arthur G. James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio.
Tom
T
Liu
Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio.
John T
JT
Patton
The Comprehensive Cancer Center and Arthur G. James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio.
Sabrina L
SL
Garman
Center for Biostatistics, The Ohio State University, Columbus, Ohio.
Xiaoli
X
Zhang
Department of Pathology, The Ohio State University, Columbus, Ohio.
Habibe
H
Kurt
Department of Pathology, The Ohio State University, Columbus, Ohio.
Gerard
G
Lozanski
Division of Infectious Disease, The Ohio State University, Columbus, Ohio.
Mark E
ME
Lustberg
The Comprehensive Cancer Center and Arthur G. James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio. Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio. Robert.baiocchi@osumc.edu Michel.caligiuri@osumc.edu.
Michael A
MA
Caligiuri
The Comprehensive Cancer Center and Arthur G. James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio. Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio. Robert.baiocchi@osumc.edu Michel.caligiuri@osumc.edu.
Robert A
RA
Baiocchi
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D015534:Trans-Activators / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
C063676:BZLF1 protein, Herpesvirus 4, Human; D015534:Trans-Activators; D019444:Vaccines, DNA