Immunization with PfEMP1-DBL1α generates antibodies that disrupt rosettes and protect against the sequestration of Plasmodium falciparum-infected erythrocytes

Chen, Qijun; Pettersson, Fredrik; Vogt, Anna; Schmidt, Berit Aydin; Ahuja, Sanjay P.; Liljeström, Peter; Wahlgren, Mats

doi:10.1016/j.vaccine.2004.02.015

Cited by 56 publications

(50 citation statements)

References 216 publications

(286 reference statements)

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“…Three mini-var genes were created (for oligonucleotides, see Table S1 in the supplemental material) combining the open reading frames of three DBL1␣ domains with the transmembrane (TM) domain of the FCR3S1.2 var1 PfEMP1 as described before (14): (i) DBL1␣ domain of FCR3S1.2 var1 PfEMP1 (11); (ii) DBL1␣ domain of PAvarO var1 PfEMP1 (32); and (iii) DBL1␣ domain encoded by var5.2 of the 3D7 P. falciparum clone (chromosome 5; PfE1640) (41). Recombinant SFV particles were produced as described previously (14).…”

Section: Methodsmentioning

confidence: 99%

“…They were randomly assigned into two groups (Table 1) Challenge of immunized rats and monkeys with iRBC. Immunized rats were challenged by intravenous infusion with various 99m technetium-labeled iRBC of parasite strains according to an established protocol (14,26). The amount of sequestered iRBC was determined by relating the count rates of the separate lungs to the whole-body count rates comparing DBL1␣-and GST-immunized animals.…”

Section: Methodsmentioning

confidence: 99%

“…The family of PfEMP1 is so far the only group of surface antigens linked to the parasites' ability to cytoadhere and sequester (2,14,26). PfEMP1 is a clonally variant antigen responsible for the antigenic variation at the iRBC surface (12,34), with an extracellular part composed of various domains.…”

mentioning

confidence: 99%

“…The Duffy binding-like domain 1␣ (DBL1␣) has the highest degree of sequence conservation among all PfEMP1 domains (18) and is an attractive candidate for the development of an anti-severe malaria vaccine. Extensive analysis of the role of PfEMP1 during sequestration has revealed the importance of this domain for binding to different host receptors on RBC and endothelial cells (13,31,40) and its role in parasite sequestration in the microvasculature (14,26,40). These interactions have been linked to severe disease (9,19,25,30), and immune responses to this PfEMP1 domain can be important for protection against severe and complicated malaria.…”

mentioning

confidence: 99%

“…They recognize the PfEMP1 on the iRBC surface, disrupt parasite autoagglutinates and rosettes, and block iRBC adhesion in vivo (14,26). Here we have studied the immunogenicity of our DBL1␣ vaccine in a novel sequestration model employing the nonhuman primate Macaca fascicularis.…”

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confidence: 99%

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

et al. 2007

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The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important virulence factor on the surface of infected erythrocytes. Naturally acquired antibodies to PfEMP1 expressed by parasites causing severe malaria are suggested to be protective and of major interest for the development of a vaccine against severe disease. In this study, the PfEMP1 expressed by a parasite clone displaying a multiadhesive phenotype associated with severe malaria was well recognized by sera of malaria semi-immune children. The efficiency of the Duffy binding-like 1␣ (DBL1␣) domain of this PfEMP1 was therefore, alone or in combination with two additional DBL1␣ domains, evaluated as a potential vaccine candidate using both a rodent model and a primate model. Antibodies against the DBL1␣ domain were generated by immunization with recombinant DBL1␣-Semliki Forest virus particles and recombinant protein and analyzed in vitro. The immunized animals were challenged in vivo with various parasite strains or clones. Immunization with the PfEMP1-DBL1␣ domain abolished the PfEMP1-dependent sequestration of the homologous strain in immunized rats and substantially inhibited parasite adhesion in immunized monkeys. Protection against sequestration of heterologous parasite strains was also confirmed by direct or indirect challenge in the rat model. These results strongly support the use of the DBL1␣ domain in the development of a vaccine targeting severe malaria.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2007

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Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) Polymorphisms

Qidwai

2021

Exploration of Host Genetic Factors Associated With Malaria

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Surface antigens of Plasmodium falciparum-infected erythrocytes as immune targets and malaria vaccine candidates

Chan

Fowkes

Beeson

2014

Cell. Mol. Life Sci.

141

147

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Understanding the targets and mechanisms of human immunity to malaria caused by Plasmodium falciparum is crucial for advancing effective vaccines and developing tools for measuring immunity and exposure in populations. Acquired immunity to malaria predominantly targets the blood stage of infection when merozoites of Plasmodium spp. infect erythrocytes and replicate within them. During the intra-erythrocytic development of P. falciparum, numerous parasite-derived antigens are expressed on the surface of infected erythrocytes (IEs). These antigens enable P. falciparum-IEs to adhere in the vasculature and accumulate in multiple organs, which is a key process in the pathogenesis of disease. IE surface antigens, often referred to as variant surface antigens, are important targets of acquired protective immunity and include PfEMP1, RIFIN, STEVOR and SURFIN. These antigens are highly polymorphic and encoded by multigene families, which generate substantial antigenic diversity to mediate immune evasion. The most important immune target appears to be PfEMP1, which is a major ligand for vascular adhesion and sequestration of IEs. Studies are beginning to identify specific variants of PfEMP1 linked to disease pathogenesis that may be suitable for vaccine development, but overcoming antigenic diversity in PfEMP1 remains a major challenge. Much less is known about other surface antigens, or antigens on the surface of gametocyte-IEs, the effector mechanisms that mediate immunity, and how immunity is acquired and maintained over time; these are important topics for future research.Electronic supplementary materialThe online version of this article (doi:10.1007/s00018-014-1614-3) contains supplementary material, which is available to authorized users.

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Immunization with PfEMP1-DBL1α generates antibodies that disrupt rosettes and protect against the sequestration of Plasmodium falciparum-infected erythrocytes

Cited by 56 publications

References 216 publications

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

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

Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) Polymorphisms

Surface antigens of Plasmodium falciparum-infected erythrocytes as immune targets and malaria vaccine candidates

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