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AIDS-CoVAC
HIV/AIDS
Framework programme: 6
Call: 3
Project number: LSHP-CT-2006-037416
EC contribution: € 958,000
Duration: 24 Months
Type: STREP
Starting date: 1st December 2006
Graphic element Generation of a Coronavirus-Based Multigene AIDS Vaccine and Evaluation in a Preclinical SIV model
Keywords: HIV, Dendritic Cells, Vaccination and Coronavirus

Summary:

Coronaviruses spread via mucosal surfaces and can infect dendritic cells (DCs). These features and their exceptional transcription strategy make them extremely promising candidate vaccine vectors to overcome known problems of current HIV vaccine approaches. The National Institutes of Health, Bethesda, USA, have granted to Partner 1, support to pursue this line of research in the murine coronavirus system due to its innovation potential and since researchers from the US have not yet started to work in this direction.

The European perspective of this project is to promote further, this specific line of research in Europe in order to pave the way for the generation of coronavirus-based HIV vaccines in humans. The AIDS-CoVAC consortium aims to generate a novel coronavirus-based HIV vaccine vector, optimised for host entry by targeting specialised antigen-presenting cells, namely DCs. Recombinant coronavirus vectors in the context of a simian model could serve as a paradigm for the development and evaluation of coronavirus-based HIV vaccines.

The consortium consists of three scientific partners with well-matched, complementary expertise and resources. Covering:

  • The knowledge on coronavirus biology, reverse genetics and vector construction
  • Ample expertise on DC-based vaccination in murine models and clinical trials
  • State-of-the-art technology to assess vector-DC interactions
  • Comprehensive experience for the evaluation of candidate AIDS vaccines, in preclinical studies in monkeys
  • Animal research facilities

The collaborative and complementary research is divided into two scientific Work Packages. WP1 involves the determination of the best suitable coronavirus spike protein for optimal vector entry into simian DCs and the analysis of vector-DC interactions. WP2 will assess the gene transfer into simian DCs in vitro and the efficacy of this vaccination approach in vivo.

Background:

HIV infection represents one of the major health threats in the developing world with millions of infected individuals suffering from immunosuppressionassociated diseases, such as opportunistic infections or infection-associated cancer.

Prevention of HIV infection in developed countries is achievable by raising public awareness of the sexual transmission pattern. Furthermore, the costly treatment of infected individuals with multiple highly efficient anti-HIV drugs is still only affordable in more industrialised countries. However, less-developed countries, mainly in Africa, require a cost-effective vaccination strategy to prevent the further spread of the infection.

The knowledge of HIV biology, generated over the last two decades has paved the way for rational vaccine design. Progress in the understanding of basic immunological mechanisms underlying antigen presentation, lymphocyte trafficking and activation, and immunological memory has been instrumental in the identification of parameters that ensure induction of protective antiviral immunity. Taken together, an HIV vaccine should.

  • Target and activate DCs
  • Contain immunodominant CTL and the cell antigens
  • Display antigenic determinants to induce broadly neutralising antibody responses
  • Be applicable via mucosal surface
  • s

Aim:

  • Develop a coronavirus-based multigene vaccine that specifically targets dendritic cells
  • Evaluate the novel approach through preclinical testing in a simian model
  • Expand the understanding of the molecular biology of coronavirusdendritic cell interaction and exploiting this knowledge for improving the novel virus vector system.

Expected results:

  1. New devices and modalities for DNA delivery to the epidermis
  2. Generate improved DNA-based vaccines combining the advantages of GTU vectors for long-term expression and plasmo-VLP vectors for the presentation of antigens onto VLPs
  3. Generation of new proprietary HIV antigens based on the EPIVAC optimised vector.

Coordinator:

1 - PD Dr. Burkhard Ludewig
Kantonsspital St. Gallen
Research Department
Rorschacherstrasse 95, CH-9007 St. Gallen
Switzerland
Tel.: 41-71-4941090,
Fax: 41-71-4946321
E-mail: Burkhard.Ludewig@kssg.ch
Website: www.lfa-sg.ch

Partners:

Principal
Scientific
Participants
Official Address Other Information
2PD Dr. Sieghart Sopper Deutsches Primatenzentrum GmbH
Kellnerweg 4,
D-37077 Göttingen
Germany
Tel: 49-551-3851383
Fax: 49-551-3851184,
E-mail: sopper@dpz.gwdg.de
Website: www.dpz.eu
3Dr. Maria Foti Universitá degli Studi di Milano-Bicocca
Dept. Biotechnology and Bioscience
Piazza dell'Ateneo Nuovo, 1'
I-20126 Milano,
Italy
Tel: 39-02-64483520,
Fax: 39-02-64483552
E-mail: maria.foti@unimib.it
Website: www.unimib.it

 
 
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