Skip to main content

Structural analysis of the CSA binding interactions involved during pregnancy associated malaria

Objective

Adhesion of Plasmodium falciparum-infected erythrocytes (PE) to placental chondroitin-4-sulfate (CSA) has been linked to the severe disease outcome of pregnancy-associated malaria (PAM). After multiple pregnancies, women acquire protective antibodies that block CSA-binding and cross-react with geographically diverse placental isolates suggesting that surface molecule(s) expressed by PAM-infected erythrocytes have conserved epitopes and that a PAM vaccine may be possible. Recent evidence strongly suggests that var2CSA, a member of the P. falciparum Erythrocyte Membrane protein 1 (PfEMP1) family, may have an important role in PAM and immunity. Although var2CSA and to some extent var1CSA are the main candidates for a pregnancy malaria vaccine, experimental evidence implies that antigenic polymorphism and the lack of a small animal in vivo experimental model may pose a challenge for vaccine development. To date, efforts to develop a truly prophylactic PAM vaccine have been hindered by the difficulty in identifying immunogens that elicit broadly neutralizing and adhesion-blocking antibodies. Accordingly, a small number of highly specialized and experienced malaria research groups from Europe (6 groups) and endemic countries (2 groups) have decided to give highest priority to decipher the molecular basis for the CSA binding to the parasite ligands in order to define the common features within the different CSA-binding domains and the cross-reactive epitopes that are likely to be the targets of natural protective antibodies. This knowledge will not only be very helpful in the design of novel PfEMP1-CSA based antigens capable of inducing broad and potent neutralising antibodies to a wide variety of strains, but also to identify molecules with inhibitory capacity that could be considered for therapeutic strategies as anti-adhesive drugs.

Field of science

  • /medical and health sciences/health sciences/infectious disease/malaria

Call for proposal

FP7-HEALTH-2007-A
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

INSTITUT PASTEUR
Address
Rue Du Docteur Roux 25-28
75724 Paris Cedex 15
France
Activity type
Research Organisations
EU contribution
€ 753 220
Administrative Contact
Graham Bentley (Mr.)

Participants (6)

INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY
Italy
EU contribution
€ 345 510
Address
Padriciano 99
34149 Trieste
Activity type
Research Organisations
Administrative Contact
Shubha Narayanan (Ms.)
KOBENHAVNS UNIVERSITET
Denmark
EU contribution
€ 334 264
Address
Norregade 10
1165 Kobenhavn
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Ivan Kristoffersen (Mr.)
UNIVERSITATSKLINIKUM HEIDELBERG
Germany
EU contribution
€ 338 251
Address
Im Neuenheimer Feld 672
69120 Heidelberg
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Thorsten Brietz (Mr.)
ACADEMISCH ZIEKENHUIS LEIDEN
Netherlands
EU contribution
€ 334 473
Address
Albinusdreef 2
2333 ZA Leiden
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Linda Ouwerkerk (Ms.)
4 SC AG
Germany
EU contribution
€ 123 003
Address
Fraunhoferstr. 22
82152 Planegg Martinsried
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Dagmar Schirm (Ms.)
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
EU contribution
€ 81 000
Address
Rue De Tolbiac 101
75654 Paris
Activity type
Research Organisations
Administrative Contact
Isabelle Pires (Ms.)