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VLP-based Epstein-Barr-Virus (EBV) vaccine

Reference Number TO 01-00833

Challenge

Epstein-Barr-Virus (EBV) is an ubiquitous human herpes virus that infects over 90% of the population world-wide with a life-long persistence. If infection is retarded and happens during adolescence or adulthood, it is regularly causing a benign, normally self-limiting lympho-proliferative syndrome termed infectious mononucleosis (IM) in up to 50% of cases. Clinical apparent IM has been found to significantly increase the risk to develop Hodgkin disease and other type of lymphoma and is an independent risk factor for multiple sclerosis (MS). In addition, EBV is causally associated with malignant diseases like nasopharyngeal carcinoma, gastric carcinoma, and various types of lymphoma. Patients with immune defects like transplant recipients are at particular risk for EBV-associated diseases as a consequence of immunosuppressive treatment. Yet, a save and efficient vaccine is not available nor approved.

Reactivation of CD4+ and CD8+ T cells from EBV-positive donors. Source: HMGU, Prof. Zeidler
Reactivation of CD4+ and CD8+ T cells from EBV-positive donors. Source: HMGU, Prof. Zeidler

Technology

The inventors provide EBV-like virus particles (VLPs) that are free of viral DNA and reliably induce strong polyvalent neutralizing humoral and cellular immune responses in naive hosts. VLPs are produced in and released from a dedicated packaging cell line that harbors an EBV helper genome from which all potential viral oncogenes have been deleted. Like wt-EBV, VLPs have an intrinsic B-cell tropism responsible for the strong EBV-specific immune responses. The VLP vaccine is able to elicit EBV-specific CD4+ and CD8+ immune responses in an animal model and in EBV-seropositive human donors. Thus, VLPs containing multiple and complex EBV antigens are a promising candidate for the first safe and efficient EBV vaccine.

Commercial Opportunity

EBV-VLPs constitute an effective and safe vaccine for individuals having any kind of serostatus. The vaccine may be used to reduce the clinical symptoms of IM and the risks for EBV-associated diseases, in particular, the risks for post-transplant EBV-associated diseases in immunocompromized patients. The current establishment of a 3rd generation packaging cell line releasing VLPs constitutively and growing in FCS-free cell culture medium is a next step towards a standardized large-scale production.

The technology is available for licensing as well as for joint collaboration for further pre-clinical validation and/or clinical development.

Developmental Status

Proof of principle has been shown in a mouse model inducing strong polyvalent neutralizing humoral and cellular immune responses. Experiments in an animal model providing convincing results in protection against EBV infection will start immediately.

Patent Situation

Patents are pending in EP, US, CN and JP (priority 2010).

Further Reading

Jochum et al. (2012), PNAS 109(21), E1396-E1404; Ruiss et al. (2011), J. Virol. 85, 13105-13113