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China-HIV-VacIII
HIV/AIDS (INCO)
Framework programme: 5
Project number:
ICA4-CT-2002-10042
EC contribution: € 1 500 000
Duration: 36 months
Type: RS
Starting date: Autumn 2002
Graphic element Phase I/II clinical testing of Clade C-based HIV-1 Candidate Vaccines in China

Summary:

The number of people living with HIV/AIDS in China is estimated to be >600 000 and projected to rise exponentially. Based on an in-depth characterisation of the epidemiological situation, three candidate vaccines (an innovative DNA vaccine and two different types of recombinant vaccinia viruses, encoding a synthetic, Chinese clade C (CN54) derived Env and GagPolNef polygene) will be tested in a phase I/II clinical trial in China. Ninety selected HIV negative volunteers will be vaccinated according to different prime/boost regimens and assessed for the safety and immunogenicity of the candidate vaccines. Emphasis will be put on the characterisation of (cross-clade) cellular and humoral immune responses towards different regional virus strains. The proposed project also aims to establish the necessary infrastructure for future field trials.

Objectives:

The primary goal of this study is to develop and to coordinate the capacity building in China as a prerequisite for future phase III field trials. Major objectives of the proposed project are (i) to broaden the molecular epidemiology basis, and (ii) to improve further the current candidate vaccines for upcoming vaccination trials. Another aim is to determine the safety and immunogenicity of the currently available DNA- and vaccinia virus-based vaccines encoding GagpolNef and Env antigens from a representative Chinese R5 isolate (CN54) in a phase I/II clinical trial in China. Furthermore, the capacity of a DNA priming immunisation to lower the dose of the following booster immunisations with either a non-replicating or replicating vaccinia strain will be determined. The project will also assess the immunigenicity of the suggested vaccination regimens for CD4 and CD8 T-cells and for the induction of neutralising Abs.

Description:

Regarding the rapid spread of the clade C HIV- 1 epidemic and in view of future field trials projected to be performed in China, a careful follow-up on the epidemiological situation will be an integral part of the proposed study. Ongoing epidemiological analysis will include the development and transfer of a new technology that significantly facilitates the access to infectious full-length molecular clones from relevant primary isolates and allows quantifying cross-clade specific immune responses as induced by the suggested vaccination strategy. An innovative DNA vaccine and a non-replicating vaccinia virus each encoding a synthetic, Chinese RS clade C (CN54) HIV-l derived Env and GagPolNef polygene have been established and already GMP manufactured (EUROVAC). A safe and replication-competent vaccinia virus (TienTan) will be established and produced according to GMP guidelines in China. This strain has originally been generated, tested, approved and used in clinical trials in China as a carrier for various viral antigens. These three candidate vaccines will be tested in a phase I/II clinical trial in China. Ninety selected HIV negative volunteers will be vaccinated at the Beijing UBMH and assessed for the safety and immunogenicity of the candidate vaccines. Emphasis will be put on the capacity of DNA priming to lower the dose of the following booster immunisations using either the non-replicating NWAC or the replicating TienTan strain. A major goal is to carefully characterise (cross-clade ) CD4+ and CD8+ cell mediated immune responses. This part also includes the training of Chinese researchers on the ELISpot and intra-cellular cytokine detection assays, currently considered as the reference methods for the evaluation of T cell responses to vaccines. The capacity of the candidate vaccines to induce (cross-)neutralising antibodies will be determined, taking advantage of standardised protocols that have been evolved in the EUROVAC programme.

Milestones:

During the course of the project, it is expected to extend the knowledge on HIV-epidemiology in China. New methodology will be developed (month 18), facilitating the generation of representative full-length molecular HIV-l clones (month 24). Based on the availability of a safe DNA vaccine and two vaccinia virus cGMP lots (month 18), new information is expected on the dosing and immunogenicity (CD4, CD8, nAbs) of antigens/immunisation regimens (month 36). Another aim of the project is to establish the necessary infrastructure to perform future field trials in China.

Coordinators:

Hans WOLF
University of Regensburg
Institute of Medical Microbiology
Franz-Josef-Strauß-Allee 11
93053 Regensburg
Germany
Tel: +49 941 944 6401
Fax: +49 941 944 6402
E-mail: hans.wolf@klinik.uni-r.de

Ralf WAGNER
University of Regensburg
Institute of Medical Microbiology
Franz-Josef-Strauß-Allee 11
93053 Regensburg
Germany
Tel: +49 941 944 6452
E-mail: ralf.wagner@klinik.uni-r.de

Partners:

  1. National Centre for Aids Prevention and Control - National Aids Reference Laboratory Beijing, China
  2. Beijing Union Medical College Hospital - Department of Infectious Disease Pumch, Beijing, China
  3. Université Pierre et Marie Curie - Laboratoire d'immunologie Cellulaire et Tissulaire Paris, France

 
 
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