Antigenic differences and conservation among placental Plasmodium falciparum-infected erythrocytes and acquisition of variant-specific and cross-reactive antibodies

Beeson, JG; Mann, EJ; Byrne, TJ; Caragounis, A; Elliott, SR; Brown, GV; Rogerson, SJ

Author(s): Beeson, JG; Mann, EJ; Byrne, TJ; Caragounis, A; Elliott, SR; Brown, GV; Rogerson, SJ;
Details: Publication Year 2006-03-01,Volume 193,Issue #5,Page 721-730
Journal Title: JOURNAL OF INFECTIOUS DISEASES
Publication Type: Journal Article
Abstract: Background. Pregnant women are infected by Plasmodium falciparum with novel antigenic phenotypes that adhere to chondroitin sulfate A (CSA) and other receptors in the placenta. The diverse and variant parasite protein P. falciparum erythrocyte membrane protein 1 (PfEMP1), which is encoded by var genes, is a ligand for CSA and a major target of antibodies associated with protective immunity. Methods. Serum samples from pregnant women exposed to malaria were tested for immunoglobulin G, adhesion-inhibitory antibodies, and agglutinating antibodies to different CSA-binding isolates expressing conserved var2csa-type genes and to parasite isolates from infected placentas. Parasite isolates also were examined to assess PfEMP1 expression, the effect of trypsin treatment of infected erythrocytes on parasite adhesion and cleavage of PfEMP1, and inhibition of adhesion by rabbit antiserum raised against a CSA- binding isolate. Results. Findings demonstrated that (1) there are significant antigenic differences between CSA- binding isolates that correspond with polymorphisms in var2csa; (2) there are differences in the properties of PfEMP1 and antibody reactivity between CSA- binding and placental isolates, which express multiple PfEMP1 forms; (3) acquired antibodies target diverse and cross-reactive epitopes expressed by CSA-binding infected erythrocytes, and cross-reactive antibodies are not necessarily cross-inhibitory; and (4) the breadth of antibody reactivity is greater among multigravidae than among primigravidae. Conclusions. Immunity may be mediated by a repertoire of antibodies to diverse and common epitopes. Strategies based on vaccination with a single domain or isolate might be hindered by antigenic diversity.
Publisher: UNIV CHICAGO PRESS
Keywords: CHONDROITIN SULFATE-A; PREGNANCY-ASSOCIATED MALARIA; SURFACE-ANTIGENS; HYALURONIC-ACID; VAR GENE; PARASITE ADHESION; DISTINCT ADHESIVE; MATERNAL MALARIA; RED-CELLS; WOMEN
Publisher's Version: https://doi.org/10.1086/500145
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2006-03-01 12:00:00