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Epstein-Barr-Virus like particle (EB-VLP) composition, its use as vaccine and stimulator to induce CD4+ and CD8+ T cells

Reference Number TO 01-EBV-VLP

Challenge

Epstein-Barr-Virus (EBV) is an ubiquitous oncogenic human herpes virus that infects more than 90% of the human population worldwide with a life-long persistence. EBV infection causes an enormous threat especially to the immune-compromised host. EBV is responsible for a number of acute and chronic, inflammatory, autoimmune and malignant disorders, which include several types of severe and life-threatening lymphoproliferative diseases in immunosuppressed patients. Patients at risk are candidates for solid organ or hematopoietic stem cell transplantation as well as patient with HIV infection. An important risk factor for EBV-associated post-transplant lymphoproliferative disease (PTLD) is seronegativity at the time of transplant. A prophylactic vaccine is thought to be the most effective step towards reducing the burden of EBV-associated malignant and non-malignant diseases. Not only PTLD but also infectious mononucleosis (IM) in children and adolescents and endemic Burkitt lymphoma are diseases that were identified as indications of a prophylactic EBV vaccine.

Characteristics of next-generation EBV-VLP
Characteristics of next-generation EBV-VLP

Technology

The researchers involved in the development of the EB-VLPs have profound knowledge in the virological field and represent clinicians highly experienced in EBV-induced diseases. Various VLPs have been generated that are essential free of or lack

  • EBV DNA or nucleic acid molecules encoding putative oncogenic proteins,
  • all viral miRNAs or nucleic acid molecules encoding miRNAs,
  • the viral packaging signal (TR element), and
  • viral genes which contribute to the transformation of human B cells or virus synthesis (e.g. EBNA-2, EBNA3A-C, BZLF-1, BFRF1A, LMP1).

The VLPs reliably induced strong polyvalent neutralizing humoral and cellular immune responses (CD4+ and CD8+) in naive hosts. Thus, VLPs containing multiple and complex EBV antigens are a promising candidate for the first safe and efficient EBV vaccine.

In addition, in vitro proof-of-concept has been provided demonstrating that EBV-antigen specific CD4+ T cells are efficiently expanded from peripheral blood of EBV-positive donors using PBMC pulsed with EB-VLPs as stimulators. In a PTLD-SCID mouse model, EBV-specific CD4+ cells delayed tumor growth as effectively as the CD8+ components.

Commercial Opportunity

EB-VLPs are structural similar to mature virions and constitute an effective and safe vaccine for individuals having any kind of serostatus. Therefore, those EB-VLPs are promising candidates for vaccination.
The technology is available for exclusive or non-exclusive 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. Strategies for supply of clinical-grade EB-VLPs and subsequent GMP production of the EB-VLPs to start clinical development are currently in discussion and will start immediately.

Patent Situation

Patents are granted in US and EP (ex vivo method for producing CD4+ T cells), patents are pending in EP and US (vaccine comprising EBV particle devoid of EBV DNA and of one or more polypeptides required for B-cell transformation), a PCT application has been filed (EB-VLP free of EBV DNA and devoid of all viral miRNA).

Further Reading

Albanese et al. (2016), PNAS 113, E6467-E6475; Tagawa et al. (2016), J. Exp. Med. 213, 2065-2080; Linnerbauer et al. (2014), PloS Pathog. 10, e1004068; Jochum et al. (2012), PNAS 109; 1396-1404; Ruiss et al. (2011), J. Virol. 85, 13105-13113; Adhikary et al. (2008), J. Virol. 82, 3903-3911.