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Prevention of hepatitis C virus (HCV) and HIV-1 co-infections through induction of potent T cell responses using prime-boost viral vector vaccine regimens (PEACHI)

Lucy Dorrell, Ellie Barnes, Matthias Hoffmann, Colm Bergin, Antonella Folgori, Patrick Schmid & Pietro Vernazza

abstract The goal of the PEACHI project funded by the European Commission (FP7 framework) is to develop simple, affordable and effective vaccine strategies that can be given alone or in combination to prevent hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1) and co-infection. The vaccines are based on novel and powerful viral vectors for in vivo delivery of antigens. The PEACHI Consortium members have employed replication-defective simian adenovirus (ChAd) and modified vaccinia virus Ankara (MVA) vector technology to develop the most immunogenic HCV and HIV-1 vaccines to date. We will assess the safety and immunogenicity of ChAd prime / MVA boost HCV vaccines in a key target group - HIV-positive individuals receiving antiretroviral therapy. These data are essential to support future efficacy studies aiming to assess protection of HIV-infected people from HCV infection. In addition, we will conduct the first phase I clinical studies using two distinct ChAd vectors simultaneously, one hosting an HCV immunogen spanning the entire NS region of HCV and the other, highly conserved HIV-1 sequences. This strategy aims to prime responses against both HCV and HIV-1 antigenic targets concurrently. Similarly, responses will be boosted simultaneously, using MVA vectors that host the respective HIV-1 and HCV immunogens.
Finally, recent work by Consortium members has shown that the immunogenicity of ChAd and MVA vectors is markedly improved when the encoded HCV immunogen is fused to mouse or human MHC class II invariant chain. This may be critical to the effectiveness of HCV vaccines in HIV-infected people and will be applicable to vaccine development for other major infectious diseases. Therefore, a large component of this project will be the first assessment of this novel technology in humans. Clinical studies will be complemented by comprehensive laboratory analyses to assess the strength and quality of vaccine-induced T cell responses using state-of-art assays, which will facilitate the discovery of surrogate markers of protective immunity.
   
project homepage http://cordis.europa.eu/search/index.cfm?fuseaction=proj....
project partner University of Oxford, UK
St. James's Hospital Dublin, Ireland
Okairos, Italy
type of project clinical studies
status ongoing - follow up
start of project 2013
responsible person Matthias Hoffmann