Epstein-Barr Virus (EBV) is a human herpesvirus that infects B cells and epithelial cells. It is one of the most abundant human pathogens in the world, infecting over 90% of the global population over the course of their lifetime. The most common disease type caused by EBV is self-limiting infectious mononucleosis, or glandular fever, which typically subsides over the course of a few months. However, like other herpesviruses, EBV is able to establish latency within host tissue, leading to life-long infection.
Whilst in the latent stages of infection and on reactivation, the virus is able to transform its host cell into tumour cells by both downregulating programmed cell death pathways and promoting uncontrolled division. Indeed, EBV was originally identified in cancerous tissue and has since been implicated in several malignancies, including Burkitt lymphoma, Hodgkin lymphoma, gastric carcinoma, nasopharyngeal carcinoma, and lymphomas in immunocompromised persons. It is now known to cause approximately 1.8% of all cancer deaths worldwide as well as being strongly associated with the development of multiple sclerosis. It is currently estimated that EBV-associated disease results in ~160,000 deaths per year.
Vaccination against EBV represents one possible avenue for treating these diseases: prevention or control of EBV infection may protect against the development of virus-associated cancers and multiple sclerosis later in life. There is, however, currently no licensed vaccine against EBV.
Our work focuses on identifying and evaluating potential viral targets for vaccination against EBV. EBV expresses an array of surface proteins important in cell receptor binding and membrane fusion which facilitates entry into host cell types. During natural infection, these are known to be robust targets of the immune system, including in the generation of neutralising antibody.
We are looking to understand what aspects of the immune responses to these proteins convey protection against infection and disease, and whether these proteins make for promising vaccine candidates. This work involves characterising antibody responses to the virus fusion machinery, including looking at the importance of conformation-specific antibodies. We are also interested in comparing immune responses to promising antigens administered using different vaccine technologies, such as viral vectors or by displaying proteins on the surface of virus-like particles, to determine which platform best displays antigen to the immune system and therefore induces the most protective response.