Description:
Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis and is associated with nearly 200,000 cancers and 140,000 deaths each year. EBV-associated cancers include Hodgkin's lymphoma, non-Hodgkin's lymphoma, Burkitt B cell lymphoma, and EBV post-transplant lymphoproliferative disease. The latent reservoir for EBV in the body is the B lymphocyte. Thus, blocking B cell infection is important for reducing EBV-related disease.
EBV can infect both B cells and epithelial cells; however, the method of entry differs between these two cell types. To initiate B cell infection, EBV glycoprotein 350 (gp350) binds to compliment receptor 2 (CR2; also known as CD21), followed by binding of glycoprotein 42 (gp42) to HLA class II molecules, which triggers fusion of EBV with the B cell, allowing virus entry into the cell. Fusion also requires the EBV proteins gH/gL, which are found complexed with gp42 as a heterotrimer, and gB. Infection of epithelial cells is initiated by the binding of the EBV protein BMRF2 to cellular integrins, followed by binding of gH/gL to ephrin receptor A2 and integrins, which triggers fusion by EBV gB.
Monoclonal antibodies that specifically bind EBV gp42 are described by this invention. The gp42-specific antibodies are capable of neutralizing EBV infection and inhibiting fusion of EBV with B cells. The monoclonal antibodies can be used for the treatment or prophylaxis of EBV infection, prevention of EBV-associated disease or infection in immunocompromised subjects, diagnosis of EBV infection, and detection of EBV in a biological sample.
This technology is available for licensing for commercial development in accordance with 35 U.S.C. 209 and 37 CFR part 404, as well as for further development and evaluation under a research collaboration.