Plasmodium falciparum Infection Elicits Both Variant-Specific and Cross-Reactive Antibodies against Variant Surface Antigens

Abstract

Naturally acquired antibodies to Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1), the variant surface antigens expressed on the surface of infected erythrocytes, are thought to play a role in protection against P. falciparum malaria. Here, we have studied the development of antibodies to PfEMP-1 in adult malaria patients living in Rourkela, India, an area with a low malaria transmission rate, and prevalence of antibodies to PfEMP-1 in residents of San Dulakudar, India, a village in which P. falciparum malaria is hyperendemic. Convalescent-phase sera from adult malaria patients from Rourkela agglutinate homologous P. falciparum isolates as well as some heterologous isolates, suggesting that they develop partially cross-reactive antibodies to PfEMP-1 following infection. Adult sera from San Dulakudar agglutinate diverse P. falciparum isolates, suggesting that they have antibodies with wide recognition of diverse PfEMP-1. Mixed-agglutination assays using pairs of P. falciparum isolates confirm the presence of both variant-specific and partially crossreactive antibodies in convalescent-phase sera from Rourkela and adult sera from San Dulakudar. Analysis of PfEMP-1 sequences suggests a molecular basis for the observed cross-reactivity.

Immunoglobulin G Isotype Responses to Erythrocyte Surface-Expressed Variant Antigens of Plasmodium falciparum Predict Protection from Malaria in African Children

“…1A). This observation is consistent with the results of numerous studies that have reported enhancements of the levels of IgG antibodies with specificity for the VSA expressed by heterologous parasite isolates in the postinfection period (5,7,12,16,29). Our data thus strongly imply that cross-reactive antibodies are a prominent feature of the profile of anti-VSA responses induced by P. falciparum malaria episodes in young African children with high and perennial levels of exposure to infection.…”

Antigenic Variation in Plasmodium falciparum : Gene Organization and Regulation of the var Multigene Family

“…Thus, ancient polymorphic segments have been carried forward into existing parasite populations, possibly from a burst of polymorphism that occurred in the common progenitor to these isolates. Small stretches of shared polymorphism have also been observed between lessconserved var genes and potentially contribute to cross-reactive antibody responses (15,108). These findings suggest that recombination of slowly mutating polymorphic segments has an important role in var gene diversification and that recombining genes may be more likely to share antigenic relationship.…”

Generation of Cross-Protective Antibodies against Plasmodium falciparum Sequestration by Immunization with an Erythrocyte Membrane Protein 1-Duffy Binding-Like 1α Domain

“…Immune responses to this antigen are crucial for the protection against severe disease, though additional surface antigens might be involved in protection (1,5,7,10,23,24). A potential vaccine candidate is the PfEMP1 of the parasite clone FCR3S1.2 studied here, which is able to bind to multiple host receptors (13,40), analyzed extensively in our in vivo sequestration model based on immunocompetent Sprague-Dawley rats.…”