Specificity and inhibitory activity of antibodies to Plasmodium falciparum aldolase.
The multiplication of Plasmodium falciparum within RBC is energy-dependent and the glucose consumption of infected RBC is increased more than 50 times over the consumption of normal RBC. High levels of glycolytic enzymes such as fructose-1,6-diphosphate aldolase (p41) have been detected in infected RBC. Expression of the cloned aldolase gene of P. falciparum in Escherichia coli resulted in an enzymatically active polypeptide with a high sp. act. and the recombinant p41 aldolase was used for enzymatic and immunologic studies reported here. The presence of antibodies against p41 in the sera of human adults partially immune to malaria and immunization experiments in monkeys suggest that p41 is implicated in protective immune response against the parasite. Therefore, we analyzed the capacity of various antisera to inhibit P. falciparum aldolase activity. It was found that anti-p41 antibodies raised in mice, rabbits, and monkeys inhibited very efficiently aldolase activity in vitro up to dilutions higher than 10(-3). In contrast none of the human sera with high levels of anti-p41 antibodies were able to inhibit parasite aldolase activity even at a dilution of 1/2. The inability of human antisera to neutralize parasite aldolase is not related to antibody titers but is probably related to the specificity of the human antibodies. This finding is discussed in relation to homology of structure of P. falciparum and mammalian aldolase and to a possible mechanism of parasite adaptation and survival in its natural host.
Department of Medicine, Geneva University Hospital, Switzerland.
I K
IK
Srivastava
M
M
Schmidt
U
U
Certa
H
H
Döbeli
L H
LH
Perrin
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D004912:Erythrocytes / Q000201:enzymology; D005634:Fructose-Bisphosphate Aldolase / Q000276:immunology*; D006801:Humans; D010963:Plasmodium falciparum / Q000201:enzymology / Q000276:immunology*; D011817:Rabbits
D000913:Antibodies, Protozoan; D005634:Fructose-Bisphosphate Aldolase