A comparison of transmission-blocking activity with reactivity in a Plasmodium falciparum 48/45-kD molecule-specific competition enzyme-linked immunosorbent assay.
Monoclonal antibodies (MAbs) 32F1 and 32F3 react with two independent epitopes of a protein doublet with molecular weights of 48 and 45 kilodaltons (kD) expressed on the surface of Plasmodium falciparum (Pfs48/45) macrogametes and zygotes; only 32F3 blocks transmission. These MAbs were used to develop a Pfs48/45-specific competition enzyme-linked immunosorbent assay (ELISA) using 32F1 to capture antigen and labeled 32F3 for quantification and analysis of the contribution of antibodies in human serum to transmission-blocking activity. A comparison analysis was used to determine agreement of competition ELISA titers and transmission-blocking activity as observed in the bioassay in three groups of serum samples: 37 from European travelers with previous exposure to malaria, 56 from gametocyte carriers, and 66 from schoolchildren from a malaria-endemic area in Cameroon. The index of agreement between outcomes of the ELISA and transmission-blocking assay in gametocyte carriers and in travelers was specifically defined as fair-to-moderate; in schoolchildren the agreement was not significant. The combined analysis of all sera showed a significant and fair-to-moderate agreement between the results of the competition ELISA and the transmission-blocking assay, with a relative specificity of 94% (of 105 cases negative in the transmission-blocking assay, 99 were also negative in the competition ELISA) and a relative sensitivity of 44% (of 54 cases positive in the transmission-blocking assay, 24 were also positive in the competition ELISA). This study shows that a positive C48/45-ELISA is indicative for transmission-blocking activity in the mosquito assay, while a negative result does not exclude transmission-blocking activity.
Roeffen
W
W
Department of Medical Microbiology, University of Nijmegen, The Netherlands.
Lensen
T
T
Mulder
B
B
Teelen
K
K
Sauerwein
R
R
Van Druten
J
J
Eling
W
W
Meuwissen
J H
JH
Beckers
P J
PJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000852:Anopheles; D000911:Antibodies, Monoclonal / Q000276:immunology; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology; D001667:Binding, Competitive; D002353:Carrier State / Q000276:immunology*; D002648:Child; D016001:Confidence Intervals; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D012680:Sensitivity and Specificity
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007106:Immune Sera