[Vaccination against malaria. Disappointments and hopes]

Abstract

After the first in vitro cultivation of Plasmodium falciparum 21 years ago, the prospect of anti-malarial vaccination arose many hopes, but, in the end, it so far has mainly given rise to doubts and disappointments. Technically, the problem is particularly difficult. Plasmodium falciparum has a very complex antigenic structure with several hundreds, if not several thousands, of different epitopes for each of the four main evolutive stages of the parasite (sporozoites, merozoites, gametocytes, ookinetes) which correspond to different phase of the infection and could be a target for vaccination. Many of these epitopes are stage-specific and some of them vary from one strain to another. Adjuvants also play a major role and can qualitatively modify the type of immune response. The immune mechanisms also differ according to the final goal: anti-Plasmodium infection or anti-disease vaccine. Over the last few years, the first clinical assays have been carried out with the Spf66 vaccine, a synthetic complex protein directed against sporozoites and merozoites. In adults and children, the first results in South America and in East Africa were modest but encouraging. Unfortunately they were not confirmed by further studies in West Africa and South-East Asia. Two new types of vaccines are under preliminary clinical evaluation. One is directed against ookinetes of Plasmodium falciparum (Pfs25 and Pfs28) and can stop the transmission from the mosquito. The other is an anti-sporozoite vaccine with a new immunogen (RTS,S) in which the circumsporozoite protein is fused to the hepatitis B surface antigen and can protect against infestation. New prospects and improvements are offered by the technique of DNA vaccines and will probably also result from better knowledge of cellular and molecular biology of the parasite which is being extensively studied (genomic structure). If new promising perspectives exist, it is particularly important to be careful to avoid such disappointments as those caused, in the past, by a too-optimistic and over-publicized presentation of some preliminary results. It is now certain that one or several malaria-vaccines will be available, but no one can seriously say when, for whom and how. In any case, it is unrealistic to hope that vaccine(s) alone will be able to eradicate such an epidemiologically complex disease as malaria. It is probable that only the coordinated use of all the techniques available (anti-vectorial protection and fight, chemoprophylaxis and chemotherapy, vaccination) will lead to success.