Prof. Wolfgang Hammerschmidt, Helmholtz Zentrum München; Prof. Reinhard Zeidler, Hospital of the Ludwig-Maximilians-University Munich (LMU); Dagmar Pich, Helmholtz Zentrum München
Epstein-Barr Virus (EBV) is a global threat to human health. There is currently no registered preventative or therapeutic vaccine to EBV infection. EBV infections may manifest acutely as infectious mononucleosis (IM, kissing disease) or as post-transplant lymphoproliferative disorders (PTLD) in immunocompromised patients. EBV is a risk to those immunosuppressed patients who are seronegative and receive a solid organ transplant. Latent EBV infection is also associated with various tumor types such as Hodgkin disease, gastric cancer, nasopharyngeal carcinoma, or Burkitt’s lymphoma among others.
Our technology enables the construction of EBV virus-like particles (EBV-VLP) that resemble native EBV virions in their immunogenicity but are depleted of packaging signals for the virus genome. The thus produced VLPs lack virus DNA and are incapable of propagating the infection. We further designed the vaccine virus genome to be depleted of viral oncogenes and additional factors that may lead to immune evasion.
PTLD and IM are vaccine indications with untapped commercial potential. The US alone has 125,000 cases of IM each year, some of which go along with hospital admission, drop-out from job or college and other socioeconomic events. Anti-CD20 reference therapy for established PTLD trade at treatment cost of $15,000.
A recombinant EBV-VLP production cell line was established and characterized, QC methods were developed and rodent immunogenicity is established. We solicited Scientific Advice from the Paul-Ehrlich Institute and acquired public funds to establish pre-GMP manufacturing and formal preclinical development up to GLP toxicology together with contract manufacturing and research organizations (CMO, CRO).
The medical use of EBV-VLPs is protected by a granted patent (EP2608806 B1) that was published as WO2012/025603. Our recent second patent application concerns the invention of miRNA-free VLP products to be used as vaccine formulation. An international PCT-application PCT/EP2017/054615 was filed on March 1, 2017 claiming priority of March 1, 2016, and published as WO2017/148928.
Albanese M, Tagawa T, Buschle A, Hammerschmidt W (2017) microRNAs of Epstein-Barr virus control innate and adaptive anti-viral immunity. J Virol 91:e01667–16. doi: 10.1128/JVI.01667-16
Ruiss R, Jochum S, Wanner G, Reisbach G, Hammerschmidt W, Zeidler R. A virus-like particle-based Epstein-Barr virus vaccine. J Virol. 2011;85(24):13105-13.