PREMALSTRUCT

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

Coordinatore	INSTITUT PASTEUR    more  Organization address address: RUE DU DOCTEUR ROUX 25-28 city: PARIS CEDEX 15 postcode: 75724 contact info Titolo: Mr. Nome: Graham Cognome: Bentley Email: send email Telefono: +33 1 45688610 Fax: +33 1 40613074
Nazionalità Coordinatore	France [FR]
Totale costo	3˙212˙892 €
EC contributo	2˙309˙721 €
Programma	FP7-HEALTH Specific Programme "Cooperation": Health
Code Call	FP7-HEALTH-2007-A
Funding Scheme	CP-FP
Anno di inizio	2008
Periodo (anno-mese-giorno)	2008-02-01   -   2011-07-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTITUT PASTEUR  Organization address address: RUE DU DOCTEUR ROUX 25-28 city: PARIS CEDEX 15 postcode: 75724 contact info Titolo: Mr. Nome: Graham Cognome: Bentley Email: send email Telefono: +33 1 45688610 Fax: +33 1 40613074	FR (PARIS CEDEX 15)	coordinator	0.00
2	4 SC AG  Organization address address: Am Klopferspitz 19 a city: Planegg-Martinsried postcode: 82152 contact info Titolo: Ms. Nome: Dagmar Cognome: Schirm Email: send email Telefono: -700803 Fax: -700832	DE (Planegg-Martinsried)	participant	0.00
3	ACADEMISCH ZIEKENHUIS LEIDEN  Organization address address: Albinusdreef 2 city: LEIDEN postcode: 2333 ZA contact info Titolo: Ms. Nome: Linda Cognome: Ouwerkerk Email: send email Telefono: -5269636 Fax: -5268315	NL (LEIDEN)	participant	0.00
4	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)  Organization address address: 101 Rue de Tolbiac city: PARIS postcode: 75654 contact info Titolo: Ms. Nome: Isabelle Cognome: Pires Email: send email Telefono: +33 1 43 62 27 16 Fax: +33 1 43 62 27 01	FR (PARIS)	participant	0.00
5	INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY  Organization address address: PADRICIANO 99 city: TRIESTE postcode: 34149 contact info Titolo: Ms. Nome: Shubha Cognome: Narayanan Email: send email Telefono: +91 11 2674 2356 Fax: +91 11 2674 2316	IT (TRIESTE)	participant	0.00
6	KOBENHAVNS UNIVERSITET	DK	participant	0.00
7	UNIVERSITAETSKLINIKUM HEIDELBERG  Organization address address: IM NEUENHEIMER FELD 672 city: HEIDELBERG postcode: 69120 contact info Titolo: Mr. Nome: Thorsten Cognome: Brietz Email: send email Telefono: +49 6221 567086 Fax: +49 6221 565460	DE (HEIDELBERG)	participant	0.00

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 Obiettivo del progetto (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.'

Introduzione (Teaser)

Malaria remains a serious health problem, especially in sub-Saharan Africa, which is home to hundreds of millions of new cases every year. An EU-funded project explored variant proteins expressed by placental parasites as targets for developing new approaches to treat malaria.