Herpesvirus Pathogenesis and Vaccine Development

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

Over 90% of adults are infected with EBV. Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with a number of B cell and epithelial cell cancers including Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. EBV is also associated with post-transplant lymphoproliferative disease and severe disease in patients with X-linked lymphoproliferative disease; no therapies are approved to prevent EBV infection in these patients. Human cytomegalovirus (HCMV) infects over half of the human population and is the most common infectious cause of birth defects. At present there are no licensed vaccines for either EBV or HCMV and hyperimmune globulin to HCMV has been of limited usefulness for prophylaxis or therapy of HCMV infections, while no such antibody product exists for EBV. In FYI 2021, we identified plasma donors with high titers of EBV gp350 and EBV B cell neutralizing antibodies. Pooled IgG isolated from these donors was compared to intravenous immunoglobulin for its ability to reduce viral load in the blood in humanized mice (that have human B cells, but not human epithelial cells) challenged with EBV. Humanized mice that received EBV hyperimmune globulin had significantly reduced EBV DNA copy numbers in the blood compared to animals that received saline control. However, while animals that received EBV hyperimmune globulin had lower EBV DNA copies than those that received intravenous immunoglobulin (which is commercially available to boost antibody levels in persons with low levels), the difference was not significant. Thus, while EBV hyperimmune globulin reduced the level of EBV DNA in the blood of humanized mice compared to intravenous immunoglobulin, the effect was modest. Therefore, additional studies will focus on development of potent EBV monoclonal antibodies for prophylaxis or therapy of EBV infections.