Background

Epstein-Barr virus (EBV) is the most common etiological agent of infectious mononucleosis (IM) and a major cause of virus-associated human cancers, predominantly lymphomas and carcinomas. EBV infection mostly occurs in early childhood and remains usually asymptomatic. However, in highly developed countries up to 50% of adolescents remain EBV-negative. Delayed EBV infections often leads to the development of IM with a median duration of 16 days and only gradual recovery. Long-lasting fatigue for several month interferes with productivity and diminishes the quality of life. Following primary infection, EBV establishes a clinically silent persistent B-cell infection in healthy individuals. Immunosuppression, typically in the setting of organ transplantation or after HIV infection, often results in increased EBV loads and a higher risk of developing EBV-associated diseases. DKFZ researchers have developed EBV virus-like particles (VLPs) that express a wide spectrum of structural viral proteins and elicit a potent cytotoxic CD4-positive T-cell response. DKFZ researchers knocked out two proteins involved in DNA packaging allowing production of VLPs completely devoid of viral DNA that offer a safe and effective preventative vaccine against EBV infection.

Technology Overview

Infection studies performed on primary resting B cells showed that these new EBV-VLPs are not transforming. Additionally, it could be shown in qPCR assays that they are free of any contaminating EBV DNA. Incubation of EBV-VLP with B cells cocultivated with EBV-specific T-cell clones elicited IFN-γ release in a dose-dependent manner that was similar in amplitude to the one observed with wildtype viruses [see further details].

In the present invention, DKFZ inventors used recombinant technology to excise two proteins (BBRF1 and BFLF1) involved in DNA packaging.

Further Details

Pavlova S, Feederle R, Gärtner K, Fuchs W, Granzow H, Delecluse HJ. An Epstein-Barr virus mutant produces immunogenic defective particles devoid of viral DNA. J Virol. 2013 Feb;87(4):2011-22.

Opportunity

DKFZ is looking for an industrial partner to further develop the preventive vaccine based on the VLPEBVs, see also DKFZ’s press release.