Towards a vaccine against asexual blood stage infection by Plasmodium falciparum.

In this paper, we will summarize the progress obtained in the malaria vaccine project developed by the Institut Pasteur groups interacting through the International Network of Pasteur Institutes over the last fifteen years. While trying to follow the progress in scientific and technological concepts and methodologies, the basic approach was still essentially the same as that followed by Pasteur and his acolytes to try to artificially reproduce the natural processes that lead to the development of immunity to infection and disease. A longitudinal study of two villages from the Sine Saloum area of Senegal, Dielmo and N'Diop, conducted in recent years by teams of the Institut Pasteur of Dakar, Senegal, in collaboration with the local ORSTOM malaria unit has led to the detailed analysis of the natural acquisition of premunition against Plasmodium falciparum malaria in endemic areas. The Saimiri model developed at the Pasteur Institute in Cayenne, was an important step forward in terms of studies on the mechanisms of action of protective antibodies and on vaccinations assays. If we accept the conclusions of the Pasteur groups' research on the experimental primate model and on the development of natural immunity (premunition) in highly endemic areas, the main inhibitor of progress in vaccine development is our poor understanding of the regulation of the immune response. Therefore, the general approaches that were followed for vaccine development must now be further explored using the continually developing tools of immunology and molecular biology, to elucidate regulations of the immune responses to the parasite, and identify the molecular mechanisms used by the parasite to generate and change antigen specificities.