Abstract
Epstein–Barr virus (EBV) was the first human tumor virus being discovered and remains to date the only human pathogen that can transform cells in vitro. 55 years of EBV research have now brought us to the brink of an EBV vaccine. For this purpose, recombinant viral vectors and their heterologous prime-boost vaccinations, EBV-derived virus-like particles and viral envelope glycoprotein formulations are explored and are discussed in this review. Even so, cell-mediated immune control by cytotoxic lymphocytes protects healthy virus carriers from EBV-associated malignancies, antibodies might be able to prevent symptomatic primary infection, the most likely EBV-associated pathology against which EBV vaccines will be initially tested. Thus, the variety of EBV vaccines reflects the sophisticated life cycle of this human tumor virus and only vaccination in humans will finally be able to reveal the efficacy of these candidates. Nevertheless, the recently renewed efforts to develop an EBV vaccine and the long history of safe adoptive T cell transfer to treat EBV-associated malignancies suggest that this oncogenic γ-herpesvirus can be targeted by immunotherapies. Such vaccination should ideally implement the very same immune control that protects healthy EBV carriers.
Highlights
The Epstein–Barr virus (EBV) is a common human γ-herpesvirus with the most potent host cell transforming capacity of all infectious disease agents in vitro [1]
The most prominent EBVassociated tumors are in addition to the still most common Sub-Saharan childhood tumor Burkitt’s lymphoma, posttransplant lymphoproliferative disease (PTLD), diffuse large B cell lymphomas (DLBCL), Hodgkin’s lymphoma, nasopharyngeal carcinoma and the 10% of gastric carcinoma that are positive for this virus [5]
Such immune protection would have to be watertight, because if it would be transient and just delay primary EBV infection, the ensuing initial encounters with the virus would carry a higher risk for infectious mononucleosis (IM) [8]
Summary
The Epstein–Barr virus (EBV) is a common human γ-herpesvirus with the most potent host cell transforming capacity of all infectious disease agents in vitro [1]. It was discovered 55 years ago in Burkitt’s lymphoma [2, 3] and is associated with epithelial-, lymphocyte- and smooth musclederived tumors in humans [4]. Early lytic EBV antigen expression has recently been recognized to enhance virus-associated tumor formation [1] These considerations identify latent and early lytic EBV antigens as promising candidates for vaccines, and envelope proteins are explored as targets of neutralizing antibody responses that could curb transmission
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