Poster Presentation Lorne Infection and Immunity 2018

Characterisation of E2-DHBVS virus-like particles as a HCV vaccine candidate (#138)

Joey McGregor 1 2 , Rob J Center 1 2 , Joshua Hardy 3 , Michael Piontek 4 , Manfred Suckow 4 , Faselli Coulibaly 3 , Andy Poumbourios 1 3 , Heidi E Drummer 1 2 3
  1. Burnet Institute, Melbourne, Australia
  2. Department of Microbiology and Immunology at the Peter Doherty Institute, The University of Melbourne, Melbourne, Australia
  3. Department of Microbiology, Monash University, Clayton, Australia
  4. ARTES Biotechnology GmBH, Langenfeld, Germany

Hepatitis C virus chronically infects more than 70 million people world-wide and causes ~350,000 deaths each year. In recent years the development and availability of new effective direct acting antivirals (DAAs) has made a significant impact to the treatment of HCV. Currently, there is no preventative HCV vaccine available. A successful HCV vaccine must afford protection against the 7 highly diverse genotypes of HCV, whereby the production of broadly neutralising antibodies is required. In this study we investigated if E2 could be incorporated onto a virus like particle and produce a low cost, highly immunogenic platform for the delivery of E2 antigens. We have previously shown that a soluble recombinant E2 immunogen that lacks three variable regions (E2D123) is able to elicit a higher titre of broadly neutralizing antibodies in comparison to the parental wild type form (E2RBD).  Using monomeric forms of E2 which were produced by converting 7 cysteine residues to alanine (E2D123A7 and E2RBDA7), we were able to fuse this to the Duck Hepatitis B Virus S (DHBVS) antigen to produce virus like particles. Immunoblotting determined the expression of E2 and S within VLPs and Negative stain electron microscopy was used to confirm particle formation. ELISA was used to confirm surface presentation of E2 and to characterise the antigenicity of VLPs towards neutralising and non-neutralising E2-specific antibodies in comparison to the soluble antigens. VLPs showed to have strong binding to neutralising antibodies and a reduced binding toward non-neutralising antibodies to that of the soluble forms. The immunogenicity of the VLPs was examined in guinea pigs and demonstrated the VLPs could generate E2 specific antibodies.