Functional analysis of Plasmodium falciparum apical membrane antigen 1 utilizing interspecies domains.

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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Healer J,Triglia T,Hodder AN,Gemmill AW,Cowman AF

doi

10.1128/IAI.73.4.2444-2451.2005

keywords:

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

2444-51

issue

4

eissn

0019-9567

issn

1098-5522

pii

73/4/2444

journal_volume

73

pub_type

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