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VIRIMAL


Malaria

Structure, Function and Vaccine Potential of the Vir Multigene Family in Malaria
Framework programme:
5
Project number:
QLK2-CT-2002-00853
EC contribution:
€ 1 196 180
Duration:
36 months
Type:
RS
Starting date:
1 September 2002
Website:
http://www.pasteur.fr/ip/easysite/pasteur/fr/themes-de-recherche-maladies/fiches-thematiques/tuberculose

Summary:

Antigenic variation is a common feature in malaria parasites and a considerable challenge facing the development of an efficient vaccine. The expression of variant antigens on the surface of the infected red blood cell plays a role in immune evasion, sequestration and the associated pathology. There are a number of multigene families in Plasmodium that code for these variant antigens and which are targets for protective immunity. Recently, a new gene family (vir) coding for a variant surface antigen has been identified in P. vivax. Homologues of vir have now been identified in a number of other malaria parasites. Using the availability of suitable model systems, the expression of vir will be studied and the host immunity investigated. This information will then be used to establish and test a suitable approach for a vir-based malaria vaccine.

Objectives:

The objectives are:

1) to determine the structure of vir genes and the extent of the vir gene repertoire in four species of Plasmodium
2) to analyse vir gene transcription in individual parasites and during the erythrocytic life cycle of the parasite
3) to determine the vir gene transcription profile during a chronic infection in four species of plasmodium
4) to locate the expression of vir in the infected erythrocyte and in other life cycle stages and to determine whether the vir proteins on viable erythrocytes are accessible to antibodies
5) to determine whether vir are immunogenic and whether the antibody response to vir alters the expression of vir in an infection or after immunisation
6) to define B and T cell epitopes of vir, and to determine whether there are responses to cross reactive or shared sequences or only to variant specific sequences
7) to determine if there is any relationship between vir expression, parasite sequestration and T cell mediated pathology. The ultimate objective is to develop a vir-based malaria vaccine.

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