EBV virus-like particles for vaccination purposes

After the successful developments of vaccines against hepatitis B and human Papilloma virus infection, the Epstein-Barr virus (EBV) and the Hepatitis C virus represent the most attractive candidates for vaccine development.

 

A viral vaccine must be safe, yet also offer protection against infection with the wild type virus. Current vaccines make frequent use of attenuated viral strains. However, due to EBV’s oncogenic potential, this approach is unlikely to be applicable to EBV.  Other vaccines consist of peptides or of single viral proteins, e.g. the EBV gp350 glycoprotein. Such approach is unlikely to be efficient with herpesviruses whose control requires a potent cellular immunity that cannot be elicited by a single soluble protein.

 

We have designed an EBV mutant that lacks proteins involved in capsid packaging. Cells infected by this mutant produce defective particles, known as virus-like particles (VLP) and light particles (LP) (See figure1). These defective particles retain all structure proteins and can elicit a T cell response (Pavlova et al. J Virol 2013) (See figure 2).

 

Current research aims at the development of in vivo models to be used in preclinical studies. On the one hand we are using humanized mice that carry a human immune system and are sensitive to EBV infection (see for example Lin et al PloS Path 2015). The aim of the project is to study the ability of EBV VLPs to prevent wild type infection. In a parallel approach, we have generated VLPs from the murid herpes virus 4 (MHV-4) and are evaluating their protective functions against wild type challenge.

Figure 1: Morphology and detection of EBV defective particles (Left panel) Electron micrographs of purified virions and virus-like particles (VLP) (Middle panel) Electron micrographs of EBV-infected cells producing virions or virus-like particles (VLP). (Right panel) EBV VLPs bound to B cells visualised by immunofluorescence. Elijah cells (1 x 105) were exposed to VLPs and stained with an antibody directed against gp350.
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Figure 2: T cell assay. BNRF1-specific T cells recognise B cells loaded with wild type (WT) virus or Virus-like particles (VLPs). B cells were pulsed with WT virus or VLPs for 20 hours and then co-cultured with BNRF1-specific T cells overnight. T cell activity was measured through an IFN-γ specific ELISA.
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