PROYECTOS EUROPEOS

CORDIS RTD-PROJECTS / © European Communities.

• Title: Novel vaccination strategies and vaccine formulations for epidemic and pandemic influenza control
  
  Objective: Annual influenza epidemic and pandemic outbreaks of influenza cause a significant disease burden and mortality in man and have high economical impact in the EU. The major drawbacks of influenza vaccines are their limited efficacy and production methods that are hard to adapt to requirements of continuously changing influenza viruses. We aim to improve the efficacy and production methods of epidemic and pandemic influenza vaccines through
  1) Improving epidemic vaccine strain selection based on retrospective and prospective analyses;
  2) Improving vaccine strain selection and reference reagents for pandemic influenza;
  3) Implementation of reverse genetics technologies to increase flexibility and yield of influenza vaccines;
  4) Use of a cell substrate for vaccine production;
  5) Use of novel antigen delivery systems. 6) Detailed examination of correlates of protection. Promising strategies will be tested in appropriate animal models.
  
  Start Date: 2002-10-01
  End Date: 2005-09-30
  Project Reference: QLK2-CT-2002-01034
  
  
• Title: Pathogenesis and improved diagnosis and control of avian influenza infections
  
  Objective: Avian Influenza is a devastating disease of poultry that has recently also been concern for human heal The last AI epidemic in the EU caused direct and indirect economic losses of over 600 million euros and resulted in the depopulation of. 14 million birds. The disease is highly contagious and has its natural reservoir in wild birds. The aims of this project are to develop EU validated rapid, diagnostic tests for the identification of infected flocks, natural reservoirs and potentially infected meat. In addition, the development and application of marker vaccines in order to reduce transmission of infection will be studied, particularly for their use in densely populated poultry areas, thus aiding animal welfare policies. The molecular basis of pathogenicity and the mechanisms involved in host susceptibility and transmission will be studied in animal models to clarify the pathogenetic aspects of this potential zoonosis.
  
  Start Date: 2002-10-01
  End Date: 2005-09-30
  Project Reference: QLK2-CT-2002-01454
  
  
• Title: Affecting folding of Influenza virus hemagglutinin
  
  Objective: The lumen of the reticulum endoplasmatic (ER) is the most specialised compartment for assisted protein folding IT provides a highly specialised environment for the controlled folding and maturation of membrane and soluble protein. Three different approaches will be used. One will follow the in vivo folding of a mod el protein in the ER while removing different components of the compartment. A second one will follow the folding of the model protein in vitro while adding different components of the ER. The third approach will be the use of proteins fragments or protein domains that fold autonomously, Influenza virus hematogglutinin (HA) will be used as a model in this project. HA is a type I transmembrane glycoprotein well characterised in terms of structure, function and intracellular transport.
  The project implies the use of different techniques like radioactive pulse-chase analysis, co-immunoprecipitations protein research in general, two-dimensional gel electrophoresis, viral expression system etc. to follow folding of the protein in viva and in vitro experiments. Also different biophysical techniques win be used to characterise fragments and domains of the protein, like circular dichorism and fluorescence spectroscopy, NMR, mass spectrometry (MS) etc. The proposal will constitute a very important contribution for our training in the study of protein folding. It will offer us the possibility to acquire knowledge of in vivo protein folding and to integrate this with our experience in the use of biophysical techniques to study protein folding in vitro. My experience in protein folding in vitro will be beneficial for the host group. Together w e can attempt to bridge the gap between in vivo and in vitro studies. We can help the host group to translate their findings to suitable biophysical methods. Since the group belongs to the Bijvoet Center, a wide range of biophysical technique will be available in neighbouring labs.
  
  Start Date: 2002-01-01
  End Date: 2003-12-31
  Project Reference: QLK2-CT-2001-51027
  
  
• Title: Preparing for an influenza pandemic
  
  Objective: Evidence from the Hong Kong chicken influenza outbreak has made us aware that were ill-prepared to produce conventional egg-grown influenza vaccines in response to a pandemic. This project will use reverse genetics to modify avian or swine influenza viruses, so that they are safe to use and grow well on mammalian cells.
  An MDCK or Vero cell vaccine will be produced from a highly pathogenic avian-virus, modified so that it is attenuated. The vaccine will be evaluated pre-clinically and clinically. We will also produce a library of reagents from a variety of avian and swine viruses for use in eggs or cell culture vaccine manufacture and develop new techniques for monitoring transmission of animal viruses to man.
  
  Start Date: 2001-09-01
  End Date: 2004-11-30
  Project Reference: QLK2-CT-2001-01786
  
  
• Title: European surveillance network for influenza in pigs
  
  Objective: Swine influenza (SI) infection causes important economic loss by lost production in fattening pigs and is probably the major cause of respiratory disease in fattening pigs in Europe. Recently, greater genetic and antigenic changes amongst SI subtypes have been observed in some EU member states in comparison with the period before. These changes seem to coincide with increased virulence and decreased protection by present, Sl-vaccines. In addition to the economic impact there is of course the public health risk posed by maintenance, evolution and emergence of influenza A viruses in pigs. The objective of this co-operative, surveillance network, that involves 14 partners from 10 countries in Europe, is to standardise and harmonise techniques and protocols for virus isolation and typing and to exchange reference material and information about recent swine influenza virus strains. The available information about recent SI field isolates will be stored in a data base and the field isolates will be deposited in a central virus bank to assure free access by all partners to information about SI in Europe and to SI virus field isolates The database will provide a preliminary epidemiological picture about SI in Europe that will be used to define first recommendations.
  
  Start Date: 2000-12-01
  End Date: 2003-11-30
  Project Reference: QLK2-CT-2000-01636
  
  
• Title: Demostration project: prove the mucosal adjuvanticity of LT mutants with influenza antigens for intranasal inmunization
  
  Start Date: 2000-02-01
  End Date: 2003-07-31
  Duration: 42 months
  Project Reference: QLK2-CT-1999-00070
  
  
• Title: EUREXpress, a European Consortium for large-scale gene expression analysis by RNA in situ hybridization
  
  Objective: The development of new, safe and highly effective adjuvants is 1 of the major issues in vaccine research. Recent studies that type I IFN acts as a powerful adjuvant.
  The project foresees 6 specific objectives:
  1)definition of the molecular mechanisms underlying the adjuvant activity of IFN;
  2)production of HIV-1 and influenza virus vaccines expressed in plants, as a novel approach for the development of edible vaccines;
  3)evaluation of the role of IFN in the development of an effective anti-HIV-1 vaccine;
  4)evaluation of the adjuvant effects of IFN for the generation of more effective anti-influenza vaccines;
  5)implementation of the use of small animal models for selected studies on human vaccine;
  6)clinical evaluation of the adjuvant efficacy of IFN-alpha in high risk individuals vaccinated against influenza virus.
  The project is structured in 5 WPs, designed to fulfil the objectives through a co-ordinated research effort involving 7 EC laboratories. On the whole, the research is expected to result in the development of novel vaccination strategies against HIV-1 and influenza virus and in new perspectives in vaccine development.
  
  Start Date: 2000-02-01
  End Date: 2003-08-01
  Project Reference: QLG2-CT-1999-00793
  
  
• Title: Development of immunogenic and safe vaccinia virus vaccines
  
  
  General Information: Vaccinia virus recombinants engineered to express foreign genes have great potential as new live vaccines against infectious diseases. Modified vaccinia virus Ankara (MVA) is a promising human vaccine candidate due to its restricted host range, avirulence in animal models, excellent safety record as a smallpox vaccine and potent immunogenicity. This proposal intends to investigate various aspects of vaccinia virus in order to improve and develop MVA as a recombinant human vaccine.
  Safety of recombinant vaccines. The molecular cell biology of MVA will be investigated and vaccinia virus proteins required for virus assembly and entry into cells will be characterised. This will lead to the identification of proteins that can be deleted from the viral genome and restrict even further the replication and dissemination of MVA in vivo. The role of vaccinia proteins that modulate the host immune response, such as soluble cytokine receptors or proteins that protect infected cells from interferon effects, will be investigated in the infected host. Deletion of these vaccinia genes may increase the susceptibility of vaccinia recomhinant to the attack of the immune system and also restlict virus spread.
  Immunogenicity of recombinant vaccines. Vaccinia recombinants that may be used in human medicine will probably have deficient replication, thus the immunogenicity of the expressed foreign antigens will need to be enhanced. The research project will use different approaches: i) to display foreign antigens at the surface of virions; ii) to determine the inlluence of vaccinia immunomodulatory proteins; and iii) to express host cytokines that can promote immune responses.
  These studies will lead to the development of safer and more immunogenic MVA recombinants, which will be tested as candidate vaccines against HIV, influenza and malaria parasite. Clinical trials with vaccinia MVA are being prepared, therefore there is an urgent need to understand at the molecular level the replication of vaccinia virus MVA and its interaction with the host immune system. This will not only improve MVA as a recombinant vaccine but will also allow us to control any problems that may arise in the field.
  
  Start Date: 1998-12-01
  End Date: 2001-06-30
  Project Reference: BIO4980456
  
  
• Title: Definition of the mechanism of antibody-mediated influenza virus infectivity neutralisation with a view to improving the efficacy of vaccination
  
  Objective: This project is concerned with the strategies for protection against influenza virus and has two main objectives:
  - to use monoclonal antibodies of defined specificity to characterise with a view to optimising the protective immune response to vaccination;
  - to understand how antibodies neutralise influenza virus infectivity.
  The outstanding characteristic of influenza viruses is their ability to cause frequent epidemics of respiratory disease; each outbreak is caused by an antigenically distinct virus. Protection against influenza is mainly achieved by vaccination; the target in this approach is the hemagglutinin (HA), a viral membrane glycoprotein with which neutralising antibodies react. The main objective of this project, potentially of direct practical interest, is to gain a better understanding at the molecular level of the strategy for vaccination against influenza. This is made possible by recent advances in the functional and structural characterisation of influenza HA.
  
  Start Date: 1997-05-01
  End Date: 2001-04-30
  Project Reference: BMH4972393
  
  
• Title: New generation vaccines based on recombinant self-replicating alphavirus rna
  
  General Information: To achieve (i) effective protective immunity, (ii) a high population response, (iii) prolonged duration of immunity, and (iv) high level of safety, novel vaccines should combine the efficacy of live (attenuated) vaccines and the safety of subunit vaccines. A vaccine resulting in antigen presentation which mimics that during natural infection by the cognate pathogen would appear have the highest probability of success.
  The present proposal presents a novel strategy of vaccine design to meet the above goals. Vaccine vectors are described which are based on a self-replicating, suicidal, recombinant RNA, originating from Semliki Forest virus (SFV). In this system, genes encoding relevant antigens are cloned into vectors which upon vaccination will transiently express the antigen within the cells of the host. Preliminary studies have already shown that this strategy results in a strong induction of the humoral and cellular arms of the immune system with sustained immunologic memory. Extensive in-depth studies are described to further characterize the immune responses for optimal design of individual vaccines. These studies will, among others, include the co-expression of antigen and cytokines and/or co-stimulatory factors. The present proposal further describes development of the SFV system to allow efficient delivery of vaccines as infectious, suicidal virus particles, as naked nucleic acids (NA) or as NA-lipid complexes. A number of vaccine candidates will be employed to test the functionality and efficacy of the SFV system as a transdisease vaccine strategy. Diverse applications will cover vaccines directed against influenza virus, flavivirus, lentivirus and papilloma virus infection as well as cancer.
  The SFV system is by design quite safe, but studies will be conducted to further address biosafety, in preparation for human trials. Work is also described for the design of scale up production of vaccine preparations. Finally, industrial links are already in place for rapid exploitation of results stemming from this Project.
  The tasks outlined in this Project proposal will comply with most, if not all, objectives set forth in the EC Biotechnology Workprogramme.
  
  Start Date: 1996-12-01
  End Date: 1999-11-30
  Project Reference: BIO4960006
  
  
• Title: Structural and functional analysis of influenza virus replicase
  
  Start Date: 1992-03-01
  End Date: 1995-02-28
  Project Reference: SC1*0688
  
  
• Title: Interaction entre un antigène viral et la réponse immunitaire humorale
  
  General Information: We propose to define and structurally interpret the molecular bases of influenza virus haemagglutinin antigenic variations; these are observed under the selective pressure of the humoral immune response. Crystallographic studies of entities involved in this process (haemagglutinin mutants, Fab fragments of antibodies specific for haemagglutinin and complexes of these with the haemagglutinin) complemented by a study of their association kinetics will allow to set this problem in a well defined frame. The affinity of a monoclonal antibody for a viral mutant selected by growth in its presence will be compared to those of the same antibody for other mutants obtained by site specific mutagenesis and located in the antigenic site this body recognizes. These results should allow us to establish whether mechanisms other than affinity lowering are involved in the selection giving rise to antigenic mutants and to analyze them.
  
  Start Date: 1991-02-01
  End Date: 1994-04-30
  Project Reference: SC1*0474