A protective monoclonal antibody recognizes an epitope in the carboxyl-terminal cysteine-rich domain in the precursor of the major merozoite surface antigen of the rodent malarial parasite, Plasmodium yoelii.
The 195-kDa major merozoite surface antigen of Plasmodium falciparum (Pf PMMSA) is a potential candidate for the development of a blood-stage malarial vaccine. We have focused on an analogous 230-kDa Ag of the rodent malarial parasite, Plasmodium yoelii, in an effort to study this protein in an experimental model system. Previously we reported the cloning and sequencing of a 2.1-kb portion of the gene encoding the carboxyl-terminal 77 kDa of the Py PMMSA. This region contained the B cell epitope recognized by mAb 302, a mAb shown to protect mice passively against P. yoelii challenge infection. To localize this B cell epitope, we have inserted various restriction fragments of the cloned Py PMMSA sequence into the bacterial expression vector pMG27NSTerm. Recombinant peptides of 74, 40, 34, 17, and 10 kDa have been produced which bear the epitope recognized by mAb 302. The results demonstrate that this B cell epitope is located within the most carboxyl-region of the Py PMMSA which contains a series of ten cysteine residues, also found in the PMMSA of P. falciparum. Further analysis showed that the reduction of disulfide bonds as well as the deletion of CYS-607 of the cloned sequence, resulted in the loss of the expression of this epitope. It is of interest that this epitope does not appear to be a dominant B cell determinant of the Py PMMSA molecule during infection. Inasmuch as this cysteine-rich domain of Py PMMSA displays considerable homology with that of Pf PMMSA, our data suggest that this region of the Pf PMMSA should be considered for inclusion in the development of a blood-stage vaccine.
Burns
J M
JM
Department of Microbiology and Immunology, Hahnemann University, Philadelphia, PA 19102.
Majarian
W R
WR
Young
J F
JF
Daly
T M
TM
Long
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000913:Antibodies, Protozoan / Q000276:immunology / Q000627:therapeutic use; D000937:Antigen-Antibody Reactions; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D002872:Chromosome Deletion; D003545:Cysteine / Q000378:metabolism; D004220:Disulfides; D000939:Epitopes / Q000276:immunology*; D008288:Malaria / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010967:Plasmodium yoelii / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D011498:Protein Precursors / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D004220:Disulfides; D000939:Epitopes; D011498:Protein Precursors; D011994:Recombinant Proteins; D003545:Cysteine