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Infection and Immunity, April 2000, p. 1964-1966, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Antibodies against the Plasmodium falciparum Receptor Binding Domain of EBA-175 Block Invasion Pathways That Do Not Involve Sialic Acids

David L. Narum,1 J. David Haynes,2,3 Steven Fuhrmann,1 Kathy Moch,4 Hong Liang,1 Stephen L. Hoffman,3 and B. Kim Lee Sim1,*

EntreMed, Inc., Rockville, Maryland 208501; Department of Immunology, Walter Reed Army Institute of Research, Washington, D.C. 20307-51002; Malaria Program, Naval Medical Research Center, Rockville, Maryland 208523; and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 212014

Received 24 September 1999/Returned for modification 28 October 1999/Accepted 30 December 1999

The 175-kDa Plasmodium falciparum erythrocyte binding protein (EBA-175) binds to its receptor, sialic acids on glycophorin A. The binding region within EBA-175 is a cysteine-rich region identified as region II. Antibodies against region II block the binding of native EBA-175 to erythrocytes. We identified a P. falciparum strain, FVO, that could not invade erythrocytes devoid of sialic acids due to prior neuraminidase treatment, and in addition, we used a strain, 3D7, that could invade such sialic acid-depleted erythrocytes. We used these two strains to study the capacity of anti-region II antibodies to inhibit FVO and 3D7 parasite development in vitro. Analysis of growth-inhibitory effects of purified FVO anti-region II immunoglobulin G (IgG) with the FVO and 3D7 strains resulted in similar levels of growth inhibition. FVO and 3D7 strains were inhibited between 28 and 56% compared to control IgG. There appeared to be no intracellular growth retardation or killing of either isolate, suggesting that invasion was indeed inhibited. Incubation of recombinant region II with anti-region II IgG reversed the growth inhibition. These results suggest that antibodies against region II can also interfere with merozoite invasion pathways that do not involve sialic acids. The fact that EBA-175 has such a universal and yet susceptible role in erythrocyte invasion clearly supports its inclusion in a multivalent malaria vaccine.

* Corresponding author. Mailing address: EntreMed, Inc., 9640 Medical Center Dr., Rockville, MD 20850. Phone: (301) 217-9858. Fax: (301) 217-9594. E-mail: kims{at}entremed.com.

Infection and Immunity, April 2000, p. 1964-1966, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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