PLASMODIUM-YOELII - THE ROLE OF THE INDIVIDUAL EPIDERMAL GROWTH FACTOR-LIKE DOMAINS OF THE MEROZOITE SURFACE PROTEIN-1 IN PROTECTION FROM MALARIA

The merozoite surface protein-1 (MSP-1) is a leading candidate for a v accine targeted at the erythrocytic stages of plasmodial parasite deve lopment. Recently, there has been increasing interest in this polypept ide, particularly in the carboxyl-terminal EGF-like domains. We have p reviously shown that this region from Plasmodium yoelli, when expresse d in native configuration, could immunize mice against an otherwise le thal challenge infection. In this model system, protection appears to be predominately mediated by antibodies. In all rodent immunization st udies to date, however, the immunogen has contained both of the postul ated EGF-like domains. We report here on the efficacy of immunization with the individual EGF-like domains from P. yoelli in elicitation of a protective host response. Although all animals developed some level of antibody in response to the various immunogens, only those animals with both EGF-like domains produced antibodies which could recognize t he native MSP-1 molecule. Antibodies generated against the individual EGF-like domains did cross-react with the double EGF-like domain struc ture, suggesting that the immunogens had retained elements of native c onfiguration. In addition, only those animals which generated antibodi es capable of recognizing native MSP-1 showed any level of protection from challenge infection. These results suggest that determinants uniq ue to the double EGF-like domain structure may be necessary for the ge neration of antibodies specific for the native configuration of MSP-1 and that these antibodies may play a significant role in protection. ( C) 1996 Academic Press, Inc.