Vaccine strategies against Epstein‐Barr virus‐associated diseases: lessons from studies on cytotoxic T‐cell‐mediated immune regulation

Abstract

Development of a vaccine against Epstein-Barr virus (EBV) is constrained by the latency phenotypes adopted by different EBV-associated diseases. Over the last few years an immense body of information on the pattern of viral gene expression in EBV-associated diseases and the role of cytotoxic T cells in the control of these diseases has accumulated. It would seem reasonable to suggest that emerging technologies are at a level where vaccine trials aimed at controlling infectious mononucleosis, post-transplant lymphoproliferative disease, nasopharyngeal carcinoma and Hodgkin's disease are justified. On the other hand, a more cautious approach may be required for the development of vaccines or immunotherapeutic strategies against Burkitt's lymphoma.

A virtual look at Epstein–Barr virus infection: Simulation mechanism

“…This burst of free virus can infect additional naive B-cells or be transmitted to a new host. The immune system mounts a cytotoxic T cell (CTL) response to the infected B-blasts and the lytic B-cells, i.e., those actively producing virus [8,9]. It also produces antibody against free virions.…”

Identification and prevalence of CD8+ T‐cell responses directed against Epstein‐Barr virus‐encoded latent membrane protein 1 and latent membrane protein 2

“…LMP2 is also considered, at least from the small numbers of LMP2-specific clones that have been detected in LCL-stimulated effector populations to be a subdominant antigen for CD8 ϩ T cell responses. However, several LMP2 epitopes have been identified, restricted through HLA alleles such as HLA-A2.1, A11, A23, A24 and B60, all located in the membrane-associated domain of the molecule [reviewed in 12,14,16]. Interestingly all of these epitopes are located in the membraneassociated domain of the molecule and some are even presented via the HLA class I pathway in TAP-negative cell lines, indicating TAP-independent processing of the LMP2 protein.…”

Boolean monomial control systems

“…This is the signal for the virus to start the lytic program and virus replication [63]. These lytically infected B cells are again vulnerable to CTL attack [57]. Newly released virions may infect new B cells or be shed into saliva to infect new hosts, but are also the target of neutralizing antibody.…”

“…EBV uses a series of distinct latent gene transcription programs, which mimic a normal B cell response to antigen, to drive the differentiation of the newly infected B cells. During this stage, the infected cells are vulnerable to attack by cytotoxic T cells (CTLs) [57]. The differentiation process takes place within so called germinal centers that are formed inside tiny ellipsoidal structures called follicles.…”