The combined epidermal growth factor‐like modules of Plasmodium yoelii Merozoite Surface Protein‐1 are required for a protective immune response to the parasite

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Abstract
Summary: We have reported previously that immunization with a bacterial recombinant protein containing the two epidermal growth factor (EGF)‐like modules of Plasmodium yoelii Merozoite Surface Protein‐1 (MSP‐1) protected miced against challenge with this malaria parasite. Bacterial plasmids containing sequences coding for the individual modules fused to glutathione S‐transferase (GST) have now been made. The fusion protein containing the combined EGF‐like modules was recognized by anti‐parasite antibodies and was immunogenic, producing high litre anti‐parasite and anti‐GST antibodies. In contrast, fusion proteins containing the two individual EGF‐like modules reacted poorly with the natural antibodies and their proteins, as well as a simple mixture of them, induced low levels of anti‐parasite antibodies despite producing high levels of anti‐GST antibody. Antibodies raised to the recombinant proteins recognized the 230 kDa MSP‐1. Groups of mice immunized with the different recombinant proteins were challenged with parasites: protection was observed in the group which had received the recombinant protein containing both modules but not in those groups immunized with the individual modules, either alone or as a mixture. These results suggest that there are important structural determinants formed by the two modules together, which are not present in either of the individual domains alone, and which are responsible for the immunogenicity of the protein or are the target of protective antibodies.