Developing a vaccine to prevent Hepatitis C infection
Over the past few years, our group has been working to develop a vaccine to prevent Hepatitis C (HCV) infection. Although new drugs are available to cure HCV it is widely accepted that vaccination will be required to eliminate HCV globally.
Our previous human studies have demonstrated the challenge that Hepatitis C viral diversity may present when developing a vaccine. First generation vaccines based on a single HCV gt1b immunogen encoded by heterologous Adenovirus, and most recently Adenovirus/MVA viral vectored technology, have been used in a prime-boost vaccination regimen, developed in collaboration with Italian biotech, Okairos.
These vaccines have generated robust HCV specific T cell responses, but showed limited cross reactivity with other HCV genotypes. Furthermore, some dominant T cell responses generated by vaccination are highly variable and non cross-reactive, even within genotype-1 infection (Swadling et al Sci Trans Med 2014, Kelly et al Hepatology 2015).
We have therefore developed a second generation of HCV vaccines which present a pan-genotypic conserved segment with immunogens encoded in the viral vector, ChAdOx1. Recent pre-clinical studies have shown these to be highly immunogenic and cross-reactive, with minimal targeting of junctional regions between gene segments (data presented at the European Liver Meeting 2016, A. Von Delft and T. Donnison). The next challenge will be to raise funding to move these findings on to human studies.
Summer 2016 has also seen the start of the first-in-man human study of an HCV vaccine with ChAd3/MVA encoding an HCV immunogen linked to a full length Class II invariant chain, as part of the EU funded PEACHI programme. If, as anticipated, this approach significantly enhances anti-viral immunity, then it might be widely applied to other infectious disease and cancer vaccines.