Reduction of disulfide bonds in Plasmodium falciparum gp195 abolishes the production of growth-inhibitory antibodies.
The role of disulfide-dependent protein conformation of the 195,000 kDa Plasmodium falciparum merozoite surface glycoprotein in the induction of biologically active antibodies was investigated. Serum samples from rabbits immunized with native gp195 had a mean ELISA titre of 1/560,000 and a mean in vitro parasite growth inhibition of 80%. In contrast, serum samples from rabbits immunized with reduced and alkylated gp195 had a mean antibody titre of 1/23,100 and did not inhibit parasite growth. These results indicate that the native structure of gp195 is essential for antigenicity, immunogenicity and induction of growth-inhibitory antibodies. Therefore, effective recombinant gp195-based vaccines may require the production of properly folded molecules resembling the native conformation.
Locher
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Department of Tropical Medicine and Medical Microbiology, John A. Burns School of Medicine, Leahi Hospital, Honolulu, HI 96816.
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D000478:Alkylation; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D000918:Antibody Specificity; D000953:Antigens, Protozoan / Q000276:immunology* / Q000378:metabolism*; D002846:Chromatography, Affinity; D004220:Disulfides / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D015151:Immunoblotting; D010084:Oxidation-Reduction; D010963:Plasmodium falciparum / Q000276:immunology* / Q000378:metabolism*; D011487:Protein Conformation; D011817:Rabbits
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D004220:Disulfides; C057273:antigen gp195, Plasmodium