Framework programme:

 7

Contract/Grant agreement number:

200889

EC contribution:

2.900.000 €

Duration:

36 months

Funding scheme:

Focused Research Project

Starting date:

02/01/2008

Web-site:

http://www.stoppam.org/

Keywords: Malaria, Plasmodium falciparum, pregnancy, var2csa, immune response

Background

Pregnancy-associated malaria (PAM) is a major public health priority for women and children (two issues of strategic importance in the Seventh Framework Programme or FP7) in developing countries. Plasmodium falciparum is the only lethal form of malaria, responsible for 95% of attacks in sub-Saharan Africa where 90% of world mortality occurs. Moreover, the impact of PAM and the potential of its prevention particularly in primigravidae is obvious. The recent introduction of intermittent preventive treatment during pregnancy in endemic areas has improved PAM prevention but it clearly depends on the level of drug resistance. Because of the very complex interactions network, control of a particular stage of host-parasite relationships offers a more pragmatic aim than infection control for a vaccine. Moreover, this innovation is independent of drug pressure, and makes it possible to develop a long-term tool to prevent PAM.

Aims and expected results

Effects of PAM on pregnant women (placental infection and anaemia), the offspring (birth weight reduction), and the infant (increased morbidity and mortality) are well known. Studies have underlined the role of P. falciparum variable surface antigens expressed on infected erythrocytes in binding to the placenta. A specific immune response against this antigen reduces the effect of PAM during latter pregnancies, making possible to develop a new preventive strategy based on the enhancement of this specific response.

The project consortium will conduct a cohort study in pregnant women and their newborns to quantify the effects of PAM and to identify a PAM vaccine candidate. The goals will be achieved through conducting cohort studies in two geographically separated areas where malaria is endemic (West and East Africa), to determine whether the pathological mechanisms and their resulting effects vary with parasite strains and/or transmission patterns. Biological samples will be collected during pregnancy and infancy in order to dissect the pathological and immune mechanisms involved in PAM, as well as to characterise phenotypically and genetically the infecting parasites, to provide a structural basis for an anti-PAM vaccine design.

The immunopathological effects will be measured in mothers and their newborns, as well as in infancy in relation to the timing of infection (events occurring during infancy are seen as a direct consequence of what happened during the in utero life of the foetus). The goals of the consortium will be attained through parasite characterisation and measurements of antibody and cellular immunological responses during pregnancy, at delivery, and selected time-points during the first year of life in peripheral, placental and umbilical cord blood, and relating the response to epidemiological data collected during cohort studies in pregnant women and their offspring. The ultimate goal of this project is to identify the most immunogenic epitopes of VAR2CSA (the major protein of P. falciparum parasites expressed at the surface of iE present in pregnant women) to be included in a first-generation candidate vaccine.

Potential applications:

It is anticipated that the product of this project will be directly applicable, and will be able to be part of the pipeline of vaccine development.

Coordinator:

Philippe Deloron
Institut de Recherche pour le Développement
Paris
France
philippe.deloron@ird.fr

Partners: