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Infection and Immunity, April 2005, p. 2444-2451, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2444-2451.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Functional Analysis of Plasmodium falciparum Apical Membrane Antigen 1 Utilizing Interspecies Domains

Julie Healer,1,2 Tony Triglia,1 Anthony N. Hodder,1 Alan W. Gemmill,3 and Alan F. Cowman1*

Walter and Eliza Hall Institute,1 Department of Medicine, University of Melbourne, Melbourne,2 Department of Clinical Psychology, Heidelberg Repatriation Hospital, Heidelberg, Victoria, Australia3

Received 27 April 2004/ Returned for modification 15 June 2004/ Accepted 21 December 2004

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.


* Corresponding author. Mailing address: 1G Royal Parade, Melbourne 3050, Australia. Phone: 61-3-9345 2555. Facsimile: 61-3-9347 0852. E-mail: cowman{at}wehi.edu.au.

Editor: J. F. Urban, Jr.


Infection and Immunity, April 2005, p. 2444-2451, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2444-2451.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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