A recombinant 15-kilodalton carboxyl-terminal fragment of Plasmodium yoelii yoelii 17XL merozoite surface protein 1 induces a protective immune response in mice.
Since the developmental stages of malarial parasites which replicate within erythrocytes are responsible for the morbidity and mortality associated with this disease, antigens produced by these stages have been proposed as candidates for a vaccine. One surface protein of merozoites (MSP-1) has been shown to immunize both rodents and primates against virulent challenge infection in experimental systems. However, little is known of relevant epitopes on the molecule, and attempts to obtain recombinant MSP-1 polypeptides in a native configuration have proven difficult. We have found that the cysteine-rich, carboxyl-terminal region of the MSP-1 protein from the rodent malarial parasite Plasmodium yoelii yoelii can be expressed in a native configuration as a fusion protein in Escherichia coli. This recombinant polypeptide containing 15 kDa of the predicted 197-kDa protein elicits antibodies in mice which recognize the native parasite MSP-1. Most significantly, both inbred and outbred mice immunized with the fusion protein in Ribi adjuvant are partially and in some cases completely protected against challenge infection with an otherwise lethal parasite strain. This is the first observation of such significant protection obtained with a small portion of the MSP-1 produced in recombinant systems.
Daly
T M
TM
Department of Microbiology and Immunology, Hahnemann University, Philadelphia, Pennsylvania 19102.
Long
C A
CA
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001483:Base Sequence; D004926:Escherichia coli; D005982:Glutathione Transferase / Q000276:immunology; D007114:Immunization; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D020066:Merozoite Surface Protein 1; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D010967:Plasmodium yoelii / Q000276:immunology*; D011498:Protein Precursors / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology
D000954:Antigens, Surface; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D011498:Protein Precursors; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase