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Infection and Immunity, January 2005, p. 422-430, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.422-430.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Allele Specificity of Naturally Acquired Antibody Responses against Plasmodium falciparum Apical Membrane Antigen 1

Alfred Cortés,1* Mata Mellombo,1 Rosella Masciantonio,2 Vince J. Murphy,2 John C. Reeder,3 and Robin F. Anders2

Papua New Guinea Institute of Medical Research, Madang,1 Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea,3 The Cooperative Research Centre for Vaccine Technology, Department of Biochemistry, La Trobe University, Melbourne, Victoria, Australia2

Received 12 July 2004/ Returned for modification 20 August 2004/ Accepted 12 September 2004

Antibody responses against proteins located on the surface or in the apical organelles of merozoites are presumed to be important components of naturally acquired protective immune responses against the malaria parasite Plasmodium falciparum. However, many merozoite antigens are highly polymorphic, and antibodies induced against one particular allelic form might not be effective in controlling growth of parasites expressing alternative forms. The apical membrane antigen 1 (AMA1) is a polymorphic merozoite protein that is a target of naturally acquired invasion-inhibitory antibodies and is a leading asexual-stage vaccine candidate. We characterized the antibody responses against AMA1 in 262 individuals from Papua New Guinea exposed to malaria by using different allelic forms of the full AMA1 ectodomain and some individual subdomains. The majority of individuals had very high levels of antibodies against AMA1. The prevalence and titer of these antibodies increased with age. Although antibodies against conserved regions of the molecule were predominant in the majority of individuals, most plasma samples also contained antibodies directed against polymorphic regions of the antigen. In a few individuals, predominantly from younger age groups, the majority of antibodies against AMA1 were directed against polymorphic epitopes. The D10 allelic form of AMA1 apparently contains most if not all of the epitopes present in the other allelic forms tested, which might argue for its inclusion in future AMA1-based vaccines to be tested. Some important epitopes in AMA1 involved residues located in domain II or III but depended on more than one domain.

* Corresponding author. Present address: Division of Parasitology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. Phone: (44) 20 8816 2402. Fax: (44) 20 8816 2730. E-mail: acortes{at}nimr.mrc.ac.uk.

Editor: W. A. Petri, Jr.

Infection and Immunity, January 2005, p. 422-430, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.422-430.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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