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Design and Testing of Novel Vaccines Against Epstein-Barr Virus

Epstein-Barr virus (EBV) is one of the most common human viruses. It is a causative agent of infectious mononucleosis and is associated with ~200 000 new cases of cancer and ~140,000 deaths annually. It is thought that a vaccine that prevents EBV infection and/or associated pathologies would have a significant clinical benefit. However, the kinds of immune responses a protective EBV vaccine would need to elicit have not been defined. Consequently it is not clear which viral antigens are ideal candidates for an EBV vaccine.

To get a better understanding of what types of antibodies a protective EBV vaccine should elicit, we isolate monoclonal antibodies targeting multiple viral proteins from people naturally infected with EBV and evaluate their ability to neutralize, or block infection of multiple cell types, and to block experimental EBV infection in animal models. We couple this with structural information to define critical sites of vulnerability on the virus. We then use this information to design and optimize vaccine antigens that can focus the immune response on key antigenic sites and evaluate their ability to elicit protective antibodies in animal models.