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Infection and Immunity, March 2004, p. 1557-1567, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1557-1567.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Fine Specificity of Serum Antibodies to Plasmodium falciparum Merozoite Surface Protein, PfMSP-1₁₉, Predicts Protection from Malaria Infection and High-Density Parasitemia

Brenda A. Okech,^1,2 Patrick H. Corran,^1,3 James Todd,¹ Amy Joynson-Hicks,¹ Chairat Uthaipibull,^4, Thomas G. Egwang,² Anthony A. Holder,⁴ and Eleanor M. Riley^1*

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine,¹ Division of Parasitology, National Institute for Medical Research, Mill Hill, London,⁴ Division of Immunobiology, National Institute for Biological Standards and Control, South Mimms, Hertfordshire United Kingdom,³ Division of Medical Parasitology and Tropical Medicine, Med Biotech Laboratories, Kampala, Uganda²

Received 25 September 2003/ Returned for modification 12 November 2003/ Accepted 1 December 2003

Antibodies to the C terminus of the Plasmodium falciparum merozoite surface protein, PfMSP-1₁₉, may inhibit merozoite invasion or block the effects of inhibitory antibodies. Here, using a competition enzyme-linked immunosorbent assay and antibody binding to wild-type and mutated recombinant proteins, we show that there are marked variations between individuals in the fine specificity of naturally acquired anti-MSP-1₁₉ antibodies. Furthermore, although neither the prevalence nor the concentration of total anti-MSP-1₁₉ antibodies was associated with resistance to malaria in African children, significant associations were observed between antibody fine specificity and subsequent risk of infection and high-density parasitemia during a follow-up period. Thus, the fine specificity of naturally acquired human anti-MSP-1₁₉ antibodies is crucial in determining their function. Future field studies, including the evaluation of PfMSP-1 vaccine trials, should include assays that explore antibody fine specificity as well as titer.

This article is dedicated to the memory of Steve Bennett, who died in March 2003 at the age of 52 years.

Editor: W. A. Petri, Jr.

Present address: Protein-Ligand Engineering and Molecular Biology Laboratory, National Center for Genetic Engineering and Biotechnology, Klong 1, Klong Luang, Pathumthani 12120, Thailand.

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