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MVACTOR
Coordination and Training Measures
Framework programme: 6
Call: 4
Project number: QLRT-2005-037536
EC contribution: € 1,000,000
Duration: 24 Months
Type: STREP
Starting date: 1st January 2007
Graphic element Host Immune Activation Optimised Vaccinia Virus Vectors for Vaccine Development
Keywords: Vector vaccines, poxvirus, vaccinia virus, innate immunity, immune stimulation, and immune evasion

Summary:

With this project, the highly attenuated modified vaccinia virus Ankara (MVA) will serve as the basis to develop a new generation of potent viral vector vaccines with optimised host immune activating properties. Specifically, the projects focus will be to identify and/or inactivate MVA gene functions that have immune inhibitory potential (e.g. counteracting interferon, interleukin, CC chemokine functions) and potentiate vector vaccine performance by virion modification and host cytokine co-expression.

Hence, the use of the outstanding research expertise and the highly competitive bioengineering capabilities of the Network will be used to establish a unique technology platform for poxviral vector design in vaccine development.

Background:

Poxviruses engineered to express foreign genes are recognized as potent delivery systems for heterologous antigens. One of these vectors, the safetytested modified MVA, a product of European vaccine research, serves worldwide as the vaccinia virus strain of choice for clinical investigations in experimental vaccination against AIDS, tuberculosis, malaria or tumour diseases. Recent work performed by the partners in this network consortium significantly increased the knowledge base on versatile gene products exploited by poxviruses to regulate virus-host interactions and to counteract innate and adaptive host immune responses.

Aim:

The MVACTOR project aims at engineering novel, safe and optimised vaccinia virus vector vaccines on the basis of recombinant vaccinia viruses, MVA expressing heterologous viral or parasite associated antigens. Its objectives are to increase the potency of MVA vectors:

  1. Rational inactivation of viral immune evasion genes
  2. Specific activation of host innate immune responses
  3. Direct presentation of target antigens
  4. Selective expression of host adjuvant genes.

Expected results:

To enable the consortium to derive state-of-the-art, second generation, safe and optimised MVA vectors with regard to superior immunogenicity and enhanced protective capacity further, to select the most promising MVACTOR vectors for future clinical evaluation as candidate vaccines.

Potential applications:

In the MVACTOR project, to further develop and optimise the MVA vectors for application as novel vaccines against poverty related disease; there will be collaboration between four highly experienced poxvirus research groups. The members of the consortium will rigorously test the concept of significantly improving the efficacy of vaccinia virus-based vaccines using several well established mouse animal models. The next generation of highly potent viral vectors will be most promising for clinical testing as prophylaxis against catastrophic and complex human diseases related to poverty such as AIDS, malaria, and tuberculosis. In addition, other potential applications include the use of these optimised vaccines for immunotherapy of infectious diseases (e.g. AIDS, hepatitis C) or cancer e.g. melanoma, breast cancer and colorectal cancer.

Coordinator:

1 - Gerd Sutter
Paul-Ehrlich-Institut
Dept. of Virology
Paul-Ehrlich-Str. 51-59
63225 Langen,
Germany
Tel: +41-6103-77-2140/41
Fax: +41-6103-77-1273
Email: sutge@pei.de
Website: http://www.pei.de

Partners:

Principal
Scientific
Participants
Official Address Other Information
2Geoffrey L. Smith Imperial College of Science, Technology and Medicine
Dept. of Virology
St Mary's Campus
Norfolk Place
London, W2 1PG,
UK
Tel: +44 (0) 207-594 3971/72
Fax: +44 (0) 207-594 3973
Email: glsmith@imperial.ac.uk
Website: http://www1.imperial.ac.uk
3Mariano Esteban Consejo Superior de Investigaciones Cientficas
Centro Nacional de Biotecnologia
Campus Universidad Autonoma
Ciudad Universitaria Cantoblanco
28049 Madrid,
Spain
Tel: +34-91-585.4553
Fax: +34-91-585.4506
Email: mesteban@cnb.uam.es
Website: http://www.cnb.csic.es
4Rafael Blasco Institute Nacional de Investigacin y Tecnologia
Agraria y Alimentaria
Dept. of Biotechnology
Ctra de A Coruna km 7.5
28040 Madrid,
Spain
Tel: +34-91-347-3913
Fax: +34-91-357-2293
Email: blasco@inia.es
Website: http://www.inia.es

 
 
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