Abstract

Epstein-Barr virus (EBV) is one of the most widespread viruses in the world; more than 90% of the planet’s adult population is infected. Symptomatic primary infection by this Herpesviridae corresponds to infectious mononucleosis (IM), which is generally a benign disease. While virus persistence is often asymptomatic, it is responsible for 1.5% of cancers worldwide, mainly B cell lymphomas and carcinomas. EBV may also be associated with autoimmune and/or inflammatory diseases. However, no effective treatment or anti-EBV vaccine is currently available. Knowledge of the proteins and mechanisms involved in the different steps of the viral cycle is essential to the development of effective vaccines. The present review describes the main actors in the entry of the virus into B cells and epithelial cells, which are targets of interest in the development of prophylactic vaccines aimed at preventing viral infection. This review also summarizes the first vaccinal approaches tested in humans, all of which are based on the gp350/220 glycoprotein; while they have reduced the risk of IM, they have yet to prevent EBV infection. The main proteins involved in the EBV latency cycle and some of the proteins involved in the lytic cycle have essential roles in the oncogenesis of EBV. For that reason, these proteins are of interest for the development of therapeutic vaccines of which the objective is the stimulation of T cell immunity against EBV-associated cancers. New strategies aimed at broadening the antigenic spectrum, are currently being studied and will contribute to the targeting of the essential steps of the viral cycle, the objective being to prevent or treat the diseases associated with EBV.

Highlights

  • Epstein-Barr virus (EBV), known as Human gammaherpesvirus 4, belongs to the Herpesviridae family and the Gammaherpesvirinae sub-family

  • The present review describes the main actors in the entry of the virus into B cells and epithelial cells, which are targets of interest in the development of prophylactic vaccines aimed at preventing viral infection

  • This review summarizes the first vaccinal approaches tested in humans, all of which are based on the gp350/220 glycoprotein; while they have reduced the risk of infectious mononucleosis (IM), they have yet to prevent EBV infection

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Summary

Prophylactic and Therapeutic EBV Vaccines

- EBV is an oncogenic virus with tropisms for B cells and epithelial cells. - gp350 vaccines reduce the risk of IM without preventing EBV infection. - EBV is an oncogenic virus with tropisms for B cells and epithelial cells. - gp350 vaccines reduce the risk of IM without preventing EBV infection. - gp350/220, gH, gL, gp, and gB glycoproteins are targets for neutralizing antibodies. - Latency proteins are involved in EBV oncogenesis. - Some lytic cycle proteins may contribute to EBV oncogenesis. - New vaccine candidates combine latency and lytic cycle antigens - Latency proteins are involved in EBV oncogenesis. - Some lytic cycle proteins may contribute to EBV oncogenesis. - New vaccine candidates combine latency and lytic cycle antigens

INTRODUCTION
VIRUS ENTRY AND PROPHYLACTIC VACCINES
The Entry of EBV Into B Cells
The Entry of EBV Into Epithelial Cells
The Tropism of EBV Infection
Other EBV Surface Glycoproteins
The EBV Latency Cycle
The EBV Lytic Cycle
Optimization of the Prophylactic Vaccines
Strategies Based on the Other EBV Glycoproteins of Interest
Optimization of the Therapeutic Vaccines
Findings
DISCUSSION
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