Strategies Involved in Developing an Effective Vaccine for EBV-Associated Diseases

Abstract

Publisher Summary This chapter first considers EBV host–virus relationships and then proceeds to discuss the immune control of EBV infection. Epstein–Barr virus (EBV) is encoded by a linear, double-stranded DNA genome of 172 kb that includes almost 100 identified open reading frames. The virus maintains a lifelong latent association with B lymphocytes and a permissive association with stratified epithelium in the oropharynx. Two major subtypes of EBV have been identified, A type and B type (also known as EBV-1 and EBV-2). It is possible to characterize three distinct forms of EBV latency (latency I, latency II, and latency III) that are distinguished on the basis of expression of EBV latent genes and promoter usage. These latency patterns or programs form a convenient means of classifying EBV-associated diseases and are the basis for vaccine development. The humoral response to EBV infection is defined in terms of a set of immunofluorescence assays that quantitatively assessed the antibody response to virus capsid antigen (VCA), membrane antigen (MA), early antigen-restricted (EA-R), early antigen-diffuse (EA-D), and EBV-induced nuclear antigens (EBNA). Significantly increased shedding of EBV in the oropharynx of immunosuppressed individuals provides evidence in support of an important role for T cells in controlling EBV infection. It is unlikely that a single vaccine that is applicable to all EBV-associated diseases will be developed in the near future. Given the variety of potential EBV targets in latency III diseases and the problems of immune recognition of latency II and latency I diseases, vaccines against infectious mononucleosis (IM) and posttransplantation lymphoproliferative disorders (PTLD) would seem to offer the best opportunity for early development. Vaccine trials against other EBV-associated diseases may need to proceed with more caution and may be dependent on the emergence of novel vaccine strategies derived from either animal models or related viruses.