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Infection and Immunity, February 2004, p. 1126-1134, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.1126-1134.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Antibodies to Malaria Peptide Mimics Inhibit Plasmodium falciparum Invasion of Erythrocytes

Joanne L. Casey,1 Andrew M. Coley,1 Robin F. Anders,2 Vince J. Murphy,2 Karen S. Humberstone,1 Alan W. Thomas,3 and Michael Foley1,2*

Cooperative Research Center for Diagnostics,1 Cooperative Research Center for Vaccine Technology, Department of Biochemistry, La Trobe University, Victoria 3086, Australia,2 Department of Parasitology, Biomedical Primate Research Center, 2280 GH Rijswijk, The Netherlands3

Received 21 August 2003/ Returned for modification 30 September 2003/ Accepted 31 October 2003

Apical membrane antigen 1 (AMA1) is expressed on the surfaces of Plasmodium falciparum merozoites and is thought to play an important role in the invasion of erythrocytes by malaria parasites. To select for peptides that mimic conformational B-cell epitopes on AMA1, we screened a phage display library of >108 individual peptides for peptides bound by a monoclonal anti-AMA1 antibody, 4G2dc1, known to inhibit P. falciparum invasion of erythrocytes. The most reactive peptides, J1, J3, and J7, elicited antibody responses in rabbits that recognized the peptide immunogen and both recombinant and parasite AMA1. Human antibodies in plasma samples from individuals exposed to chronic malaria reacted with J1 and J7 peptides and were isolated using immobilized peptide immunoadsorbents. Both rabbit and human antibodies specific for J1 and J7 peptides were able to inhibit the invasion of erythrocytes by P. falciparum merozoites. This is the first example of phage-derived peptides that mimic an important epitope of a blood-stage malaria vaccine candidate, inducing and isolating functional protective antibodies. Our data support the use of J1 and J7 peptide mimics as in vitro correlates of protective immunity in future AMA1 vaccine trials.

* Corresponding author. Mailing address: Department of Biochemistry, La Trobe University, Victoria 3086, Australia. Phone: 61-3-94792158. Fax: 61-3-9472467. E-mail: m.foley{at}latrobe.edu.au.

Editor: S. H. E. Kaufmann

Infection and Immunity, February 2004, p. 1126-1134, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.1126-1134.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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