Functional analysis of Plasmodium falciparum apical membrane antigen 1 utilizing interspecies domains
Details
Publication Year 2005-04,Volume 73,Issue #4,Page 2444-2451
Journal Title
INFECTION AND IMMUNITY
Publication Type
Journal Article
Abstract
Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading malaria vaccine candidate whose function has not been unequivocally defined. Partial complementation of function can be achieved by exchanging the AMA1 of P.falciparum (PfAMA1) with that of P. chabaudi (PcAMA1). In this study, parasites expressing chimeric AMA1 proteins were created to identify domains of PfAMA1 critical in erythrocyte invasion and which are important immune targets. We report that specific chimeric AMA1 proteins containing domains I to III from PfAMA1 and PcAMA1 were able to complement PfAMA1 function in erythrocyte invasion. We demonstrate that domain III does not contain dominant epitope targets of antibodies raised against Escherichia coli expressed and refolded PfAMA1 ectodomain. Furthermore, we generated a parasite line in which the N-terminal pro region of PfAMA1 does not undergo proteolytic cleavage and show that its removal is necessary for PfAMA1 function.
Publisher
AMER SOC MICROBIOLOGY
Keywords
ANTIBODY-MEDIATED INHIBITION; MALARIA VACCINE CANDIDATE; BLOOD-STAGE MALARIA; ERYTHROCYTE INVASION; MEROZOITES; AMA-1; GENE; EXPRESSION; PROTECTION; INDUCTION
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Creation Date: 2005-04-01 12:00:00
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