More effective malaria vaccines could now be developed thanks to a new approach for mining the genomic sequence of Plasmodium falciparum, which has led to the identification of new antigens with enhanced immunogenicity.

It is possible to generate protection against malaria by immunization with sporozoites (the infectious form of P. falciparum injected by the mosquito) that have been attenuated by radiation, so justifying the search for a malaria vaccine. However, the antigens mediating this protective immunity induced by vaccination with the whole organism are unknown. It is unlikely that a vaccine directed against a single antigen will be protective, so multivalent vaccines that combine antigens expressed at different stages of the parasite life cycle have been developed.

The search for further parasite antigens has been aided by the availability of the genomic sequence of P. falciparum, as well as the elucidation of the P. falciparum proteome. Here, Doolan et al. combine bioinformatic epitope predictions and in vitro cellular assays to identify new malaria target antigens.

First, multidimensional protein identification technology was used to identify 27 open-reading frames that encode antigens that are potentially expressed by the sporozoite and intra-hepatic stages of the parasite life cycle. Of these, antigens with predicted HLA-binding capacities were tested, together with four previously identified P. falciparum antigens, for reactivity with peripheral-blood mononuclear cells from volunteers who had been immunized with radiation-attenuated P. falciparum sporozoites or from control volunteers. Sixteen of the proteins were recognized as antigens by the volunteers immunized with irradiated sporozoites, but not by the controls. The immune response directed against some of the newly identified antigens was higher that that observed for the previously identified P. falciparum-derived protein antigens, indicating that these might be better candidates for vaccine development.

The approach used here shows how complex the immune response to P. falciparum is, and also validates this approach for the identification of new target antigens, which could be used in multiantigen vaccines for malaria.