PEACHI

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

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 Obiettivo del progetto (Objective)

'The goal of the PEACHI project 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.'

Descrizione progetto (Article)

Combination antiretroviral therapy has led to a dramatic improvement in life expectancy for people with HIV infection. However, co-infection with HCV remains a significant challenge. HCV is a major cause of chronic liver disease and cancer worldwide and is a leading cause of death in HIV co-infected individuals.

To address this health issue, scientists on the EU-funded http://www.peachi.eu/ (PEACHI) project are developing vaccines to prevent HCV, HIV-1 and co-infection. They are employing simian adenovirus and modified vaccinia virus Ankara vector technology to stimulate potent immune responses to HIV-1 and HCV. The vaccines have been designed to focus the immune response towards conserved regions within HIV-1 and epitope-rich regions within HCV non-structural proteins. They will evaluate the safety and efficacy of these vaccines in healthy individuals without HIV-1 or HCV infections first, followed by HIV-1 positive HCV-uninfected adults who receive ART. Single-cell analyses will be performed to assess the quality of vaccine-induced T cell responses.

The PEACHI consortium is also working on a novel vaccine technology that aims to improve the immunogenicity of existing vaccines. Their approach involves the use of a vaccine-encoded adjuvant, the human leukocyte antigen (HLA) class II-associated invariant chain, which is fused to the HCV proteins, and enhances HCV antigen presentation to immune cells.

PEACHI scientists have focused initially on vaccine development and optimisation of the clinical trial protocols, together with training in good clinical practice, laboratory techniques and standard operating procedures. Efforts are ongoing to develop and optimise new immunology assays for analysis of the clinical trial samples. These should contribute significantly to the project objectives and may open new avenues for research into immune control of HIV-1 and HCV infections.