Team:Wageningen UR/ModifyingtheHepatitisB

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Part 2: Modifying the Hepatitis B VLP for Vaccine Production

Introduction

In the world of vaccines, the story of production is a complex story that is different for every vaccine. Vaccines are produced with approaches fixed on the disease. The lack of flexibility in the production of novel vaccines gives possibility for new pathogens to arise as pandemic diseases. The influenza vaccine is a good example for this. We know that influenza viruses can create combinations out of 19 different Heamagglutinin (H) with 9 different Neuraminidase (N) receptors , used in the viral infection cycle and by the immune system for recognition. Though influenza is a well-known virus, fear of deadly pandemics from this known virus is still present, as seen in the hysteria concerning the Mexican pig flu . Reason for this is the slow production and verification of vaccines in response. While the H1N1 viral variant was lab confirmed as early as April 2009, it was not until November 2009 that vaccination started. This means that the southern hemisphere was forced to combat the new flu virus with inhibiting medicines instead of protective immunization.

The focus for the Hepatitis B VLP will be on vaccine production as final application. The final goal is to obtain a modified and bricked VLP containing an epitope. As a proof of principle we will link GFP to the outside and check the GFP with ELISA. GFP will be attached on the outside in two different ways: By fusion to the monomer of the VLP and via the K/E coil system.

Aims: Attach epitopes to the outside of the Hepatitis B VLP in order to make vaccines for pathogens other than Hepatitis B. Giving a proof of principle with GFP. Compare two different ways of attaching the GFP to the outside of the VLP.

Outside Modification of the Hepatitis B VLP

The focus will be on providing a universal approach for a connector system. The aim is to create a “Plug 'N Apply System". The concept is that only the epitopes need to be selected and produced, after which they can be applied upon one standard vaccination platform. These epitopes are fused to connector peptides. The production will be one standardized synthetic biology procedure, and produced in a single, production friendly organism. The connector peptide is able to “plug onto” a standardized platform, which then provides an expression surface ready for immunization of subjects. The standardized platform can be produced as a bulk reservoir to provide massive reserves of backbone for a sudden explosive demand of vaccine. The industry can shift their production according to the demand by solely selecting the epitope that they fuse to the connector. This will provide more flexibility and quicker response to emerging pathogenic threats

Inside Modification of the Hepatitis B VLP