THE COMBINED EPIDERMAL GROWTH FACTOR-LIKE MODULES OF PLASMODIUM-YOELII MEROZOITE SURFACE PROTEIN-1 ARE REQUIRED FOR A PROTECTIVE IMMUNE-RESPONSE TO THE PARASITE

We have reported previously, that immunization with a bacterial recomb inant protein containing the two epidermal growth factor (EGF)-like mo dules of Plasmodium yoelii Merozoite Surface Protein-1 (MSP-1) protect ed miced against challenge with this malaria parasite. Bacterial plasm ids containing sequences coding for the individual modules fused to gl utathione S-transferase (GST) have now been made. The fusion protein c ontaining the combined EGF-like modules was recognized by anti-parasit e antibodies and was immunogenic, producing high titre antiparasite an d anti-GST antibodies. In contrast, fusion proteins containing the two individual EGF-like modules reacted poorly with the natural antibodie s and their proteins, as well as a simple mixture of them, induced low levels of anti-parasite antibodies despite producing high levels of a nti-GST antibody. Antibodies raised to the recombinant proteins recogn ized the 230 kDa MSP-1. Groups of mice immunized with the different re combinant proteins were challenged with parasites: protection was obse rved in the group which had received the recombinant protein containin g both modules but not in those groups immunized with the individual m odules, either alone ol as a mixture. These results suggest that there are important structural determinants formed by the two modules toget her, which are not present in either of the individual domains alone, and which ave responsible for the immunogenicity of the protein or are the target of protective antibodies.