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Infection and Immunity, February 2004, p. 735-741, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.735-741.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Measurement of Antibody Levels against Region II of the Erythrocyte-Binding Antigen 175 of Plasmodium falciparum in an Area of Malaria Holoendemicity in Western Kenya

U.S. Army Medical Research Unit and Kenya Medical Research Institute,¹ Department of Zoology, Kenyatta University, Nairobi, Kenya,³ Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana,² Department of Immunology, Walter Reed Army Institute of Research, Silver Spring,⁴ Department of Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland⁵

Received 20 July 2003/ Returned for modification 29 September 2003/ Accepted 27 October 2003

Region II of the 175-kDa erythrocyte-binding antigen (EBA-175RII) of Plasmodium falciparum is functionally important in sialic acid-dependent erythrocyte invasion and is considered a prime target for an invasion-blocking vaccine. The objectives of this study were to (i) determine the prevalence of anti-EBA-175RII antibodies in a naturally exposed population, (ii) determine whether naturally acquired antibodies have a functional role by inhibiting binding of EBA-175RII to erythrocytes, and (iii) determine whether antibodies against EBA-175RII correlate with immunity to clinical malaria. We treated 301 lifelong residents of an area of malaria holoendemicity in western Kenya for malaria, monitored them during a high-transmission season, and identified 33 individuals who were asymptomatic despite parasitemia (clinically immune). We also identified 50 clinically susceptible individuals to serve as controls. These 83 individuals were treated and monitored again during the subsequent low-transmission season. Anti-EBA-175RII antibodies were present in 98.7% of the individuals studied. The antibody levels were relatively stable between the beginning and end of the high-transmission season and correlated with the plasma EBA-175RII erythrocyte-binding-inhibitory activity. There was no difference in anti-EBA-175RII levels or plasma EBA-175RII erythrocyte-binding-inhibitory activity between clinically immune and clinically susceptible groups. However, these parameters were higher in nonparasitemic than in parasitemic individuals at enrollment. These results suggest that although antibodies against EBA-175RII may be effective in suppressing some of the wild parasite strains, EBA-175RII is unlikely to be effective as a monovalent vaccine against malaria, perhaps due to allelic heterogeneity and/or presence of sialic acid-independent strains.

This work is dedicated to the memory of Eunita Ohas, a bright star whose light shined too briefly but will be missed by many colleagues and friends.

Editor: W. A. Petri, Jr.

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