Plasmodium falciparum: A Comparison of the Activity of Pfs230-Specific Antibodies in an Assay of Transmission-Blocking Immunity and Specific Competition ELISAs

Abstract

The activity of monoclonal antibodies (mAbs) that specifically recognize the Plasmodium falciparum sexual stage-specific protein Pfs230 was analyzed. All mAbs reacted with the surface of extracellular sexual forms of the parasite in a suspension immunofluorescence antibody reaction and precipitated the Pfs230 protein from an NP-40 extract of surface radioiodinated macrogametes/zygotes. Only mAb that bound complement blocked transmission, whereas mAb that did not bind complement but competed with the complement binding mAb for binding to the same epitope did not block transmission. These mAbs were used to develop Pfs230-specific competition ELISAs to analyze epitope diversity and to analyze the binding characteristics of anti-Pfs230 antibodies in human serum. Transmission-blocking (TB) antibodies in test/field sera competed in the competition ELISA for binding with epitope-specific, labeled mAbs against Pfs230. At least five different epitope regions could be defined with the competition ELISAs. All 46 sera from gametocyte carriers immunoprecipitated the Pfs230 molecule, while 19 of these sera blocked transmission in the bioassay. Five of the transmission-blocking and one of the nonblocking sera competed with monoclonal antibodies. A method comparison analysis was used to determine agreement between reactions in a competitive ELISA and the TB activity examined in the bioassay. The index of agreement κ between outcomes of the bioassay and ELISA was fair to poor (κ = 0.25) but since its range includes values below 0 the relation between the data obtained by the bioassay and the competition ELISA can be explained by chance alone. The serological data did not reveal a correlation between immunoprecipitation of Pfs230 and TB activity.