This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cortés, A. Articles by Anders, R. F. Search for Related Content PubMed PubMed Citation Articles by Cortés, A. Articles by Anders, R. F.

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

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.

Editor: W. A. Petri, Jr.

This article has been cited by other articles:

• Remarque, E. J., Faber, B. W., Kocken, C. H. M., Thomas, A. W. (2008). A Diversity-Covering Approach to Immunization with Plasmodium falciparum Apical Membrane Antigen 1 Induces Broader Allelic Recognition and Growth Inhibition Responses in Rabbits. Infect. Immun. 76: 2660-2670 [Abstract] [Full Text]  
• Miura, K., Zhou, H., Muratova, O. V., Orcutt, A. C., Giersing, B., Miller, L. H., Long, C. A. (2007). In Immunization with Plasmodium falciparum Apical Membrane Antigen 1, the Specificity of Antibodies Depends on the Species Immunized. Infect. Immun. 75: 5827-5836 [Abstract] [Full Text]  
• Faber, B. W., Remarque, E. J., Morgan, W. D., Kocken, C. H. M., Holder, A. A., Thomas, A. W. (2007). Malaria Vaccine-Related Benefits of a Single Protein Comprising Plasmodium falciparum Apical Membrane Antigen 1 Domains I and II Fused to a Modified Form of the 19-Kilodalton C-Terminal Fragment of Merozoite Surface Protein 1. Infect. Immun. 75: 5947-5955 [Abstract] [Full Text]  
• Dutta, S., Lee, S. Y., Batchelor, A. H., Lanar, D. E. (2007). Structural basis of antigenic escape of a malaria vaccine candidate. Proc. Natl. Acad. Sci. USA 104: 12488-12493 [Abstract] [Full Text]  
• Coley, A. M., Parisi, K., Masciantonio, R., Hoeck, J., Casey, J. L., Murphy, V. J., Harris, K. S., Batchelor, A. H., Anders, R. F., Foley, M. (2006). The Most Polymorphic Residue on Plasmodium falciparum Apical Membrane Antigen 1 Determines Binding of an Invasion-Inhibitory Antibody.. Infect. Immun. 74: 2628-2636 [Abstract] [Full Text]