Variant surface antigens of Plasmodium falciparum and their roles in severe malaria

2017 ◽  
Vol 15 (8) ◽  
pp. 479-491 ◽  
Author(s):  
Mats Wahlgren ◽  
Suchi Goel ◽  
Reetesh R. Akhouri
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Surface Antigens ◽  
Variant Surface Antigens

In vitro selection of Plasmodium falciparum 3D7 for expression of variant surface antigens associated with severe malaria in African children

2003 ◽  
Vol 25 (8-9) ◽  
pp. 421-427 ◽  
Author(s):  
Trine Staalsoe ◽  
Morten A. Nielsen ◽  
Lasse S. Vestergaard ◽  
Anja T. R. Jensen ◽  
Thor G. Theander ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
In Vitro Selection ◽  
Surface Antigens ◽  
Variant Surface Antigens ◽  
African Children ◽  
Selection Of

scholarly journals Immunoglobulin G Isotype Responses to Variant Surface Antigens of Plasmodium falciparum in Healthy Gabonese Adults and Children during and after Successive Malaria Attacks

2004 ◽  
Vol 72 (1) ◽  
pp. 284-294 ◽  
Author(s):  
Gerardo Cabrera ◽  
Clarisse Yone ◽  
Anne E. Tebo ◽  
Jan van Aaken ◽  
Bertrand Lell ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immunoglobulin G ◽  
Surface Antigens ◽  
Healthy Adults ◽  
Healthy Children ◽  
Variant Surface Antigens ◽  
Age Related ◽  
Adults And Children ◽  
The Individual ◽  
Malaria Episodes

ABSTRACT We assessed immunoglobulin G (IgG) isotype responses with specificity for the variant surface antigens (VSA) of heterologous Plasmodium falciparum isolates by using flow cytometry and plasma from healthy Gabonese adults and from children during and after two consecutive malaria episodes. The individual isolate-specific antibody profiles differed markedly in terms of their isotype content but were similar for healthy adults and healthy uninfected children. In healthy adults, IgG3 and IgG2 responses were the highest, while in healthy children, IgG3 and IgG4 predominated. A transiently elevated IgG1 response was observed during the second of two successive malaria episodes in children, signaling P. falciparum infection-induced cross-reactive anti-VSA responses. Our findings highlight the prominence of IgG3 in the overall profile of these responses but also indicate a marked age-related increase in the prevalence of anti-VSA antibodies of the classically noncytophilic IgG2 isotype, possibly reflecting the high frequency of the histidine-131 variant of FcγRIIA in the Gabonese population.

scholarly journals Temporal Expression and Localization Patterns of Variant Surface Antigens in Clinical Plasmodium falciparum Isolates during Erythrocyte Schizogony

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49540 ◽  
Author(s):  
Anna Bachmann ◽  
Michaela Petter ◽  
Ann-Kathrin Tilly ◽  
Laura Biller ◽  
Karin A. Uliczka ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Antigens ◽  
Temporal Expression ◽  
Variant Surface Antigens

scholarly journals Placental Malaria Induces Variant-Specific Antibodies of the Cytophilic Subtypes Immunoglobulin G1 (IgG1) and IgG3 That Correlate with Adhesion Inhibitory Activity

2005 ◽  
Vol 73 (9) ◽  
pp. 5903-5907 ◽  
Author(s):  
Salenna R. Elliott ◽  
Amy K. Brennan ◽  
James G. Beeson ◽  
Eyob Tadesse ◽  
Malcolm E. Molyneux ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Inhibitory Activity ◽  
Placental Malaria ◽  
Surface Antigens ◽  
Phagocytic Cells ◽  
Specific Antibodies ◽  
Variant Surface Antigens ◽  
And Control ◽  
Chondroitin Sulfate A ◽  
In Pregnancy

ABSTRACT Antibodies targeting variant antigens on the surfaces of chondroitin sulfate A (CSA)-binding malaria-infected erythrocytes have been linked to protection against the complications of malaria in pregnancy. We examined the isotype/subtype profiles of antibodies that bound to variant surface antigens expressed by CSA-adherent Plasmodium falciparum in pregnant Malawian women with and without histologically defined placental malaria. Women in their first pregnancy with placental malaria produced significantly greater amounts of immunoglobulin G1 (IgG1) and IgG3 reactive with surface antigens of malaria-infected erythrocytes than uninfected women of the same gravidity. IgG1 and IgG3 levels in infected and control women in later pregnancies were similar to those in infected women in their first pregnancy. Levels of IgG2 and IgG4 were similarly low in infected and uninfected women of all gravidities. IgM that bound to the surface of CSA-adherent P. falciparum occurred in all groups of women and malaria-naïve controls. There was a significant correlation between IgG1 and IgG3 levels, indicating that women usually produced both subtypes. Levels of IgG1 and IgG3 correlated with the ability of serum or plasma to inhibit parasite adhesion to CSA. Taken together, these data suggest that IgG1 and IgG3 dominate the IgG response to placental-type variant surface antigens. They may function by blocking parasite adhesion to placental CSA, but given their cytophilic nature, they might also opsonize malaria-infected erythrocytes for interaction with Fc receptors on phagocytic cells.

scholarly journals Effects of Pregnancy and Intensity of Plasmodium falciparum Transmission on Immunoglobulin G Subclass Responses to Variant Surface Antigens

2005 ◽  
Vol 73 (7) ◽  
pp. 4112-4118 ◽  
Author(s):  
Rosette Megnekou ◽  
Trine Staalsoe ◽  
Diane W Taylor ◽  
Rose Leke ◽  
Lars Hviid
Keyword(s):  
Plasmodium Falciparum ◽  
Gestational Age ◽  
Immunoglobulin G ◽  
Surface Antigens ◽  
Transmission Intensity ◽  
Parasite Transmission ◽  
Variant Surface Antigens ◽  
Pregnancy Status ◽  
Immunoglobulin G Subclass ◽  
Very High

ABSTRACT Placenta-sequestering Plasmodium falciparum involved in the pathogenesis of pregnancy-associated malaria (PAM) in otherwise clinically immune women expresses particular variant surface antigens (VSAPAM) on the surface of infected erythrocytes that differ from VSA found in parasitized nonpregnant individuals (non-PAM type VSA). We studied levels of immunoglobulin G (IgG) and IgG subclasses with specificity for VSAPAM and for non-PAM type VSA in pregnant and nonpregnant women from two sites with different endemicities in Cameroon. We found that VSAPAM-specific responses depended on the pregnancy status, parity, gestational age, and parasite transmission intensity, whereas only the parasite transmission intensity influenced the levels of IgG specific for non-PAM type VSA. For both types of VSA, the responses were dominated by the cytophilic subclass IgG1, followed by IgG3. In pregnant women, the levels of VSAPAM-specific antibodies either were very low or negative or were very high, whereas the levels of the antibodies specific for non-PAM type VSA were uniformly high. Interestingly, the levels of VSAPAM-specific IgG1 increased with increasing gestational age, while the levels of the corresponding IgG3 tended to decrease with increasing gestational age. The IgG subclass responses with specificity for non-PAM type VSA did not vary significantly with gestational age. Taken together, our data indicate that IgG1 and to a lesser extent IgG3 are the main subclasses involved in acquired VSAPAM-specific immunity to pregnancy-associated malaria.

scholarly journals The Association of High Prevalence of Trophozoites in Peripheral Blood with Lower Antibody Response toP. falciparumInfected Erythrocytes among Asymptomatic Children in Sudan

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Sara N. Mohamed ◽  
Dina A. Hassan ◽  
Abdelrahim M. El Hussein ◽  
Ihssan M. Osman ◽  
Muntasir E. Ibrahim ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Plasmodium Falciparum ◽  
Peripheral Blood ◽  
Surface Antigens ◽  
Igg Antibodies ◽  
Autologous Plasma ◽  
Variant Surface Antigens ◽  
Asymptomatic Children ◽  
Infected Rbcs ◽  
The Mean

Background. The most prominent variant surface antigens (VSAs) ofPlasmodium falciparumare the var gene-encodedPlasmodium falciparumerythrocyte membrane protein 1 (PfEMP1) family, which serves as a parasite-sequestering ligand to endothelial cells. In this study we have examined the antibody reactivity of autologous plasma from symptomatic and asymptomatic malaria infected children against the infected erythrocytes’ surface antigens using flow cytometry.Methods. Ethidium-bromide-labelled erythrocytic mature forms ofP. falciparumparasites obtained from symptomatic and asymptomatic children were sequentially incubated with autologous plasma and fluorescein isothiocyanate-conjugated (FITC) antihuman IgG. Plasma antibody reactivity was detected by flow cytometry.Results. Asymptomatic children had more prevalence of trophozoites in peripheral blood (66%) compared to symptomatic children (16%),p=0.002. The mean percentage of infected RBCs reacting with autologous sera was 89.78 among symptomatic children compared to 79.62 among asymptomatic children (p=0.09). Moreover, the mean fluorescence intensity (MFI) in the asymptomatic was significantly higher compared to symptomatic children (pvalue = 0.040).Conclusion. Variant surface antigens onPlasmodium falciparuminfected RBCs from symptomatic malaria children tend to be better recognized by IgG antibodies. This may suggest a role of some IgG antibodies in severity of malaria.

scholarly journals Antibody Recognition of Plasmodium falciparum Erythrocyte Surface Antigens in Kenya: Evidence for Rare and Prevalent Variants

1999 ◽  
Vol 67 (2) ◽  
pp. 733-739 ◽  
Author(s):  
Peter C. Bull ◽  
Brett S. Lowe ◽  
Moses Kortok ◽  
Kevin Marsh
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Inverse Relationship ◽  
Infected Erythrocyte ◽  
Surface Antigens ◽  
Maternal Antibodies ◽  
Antibody Repertoire ◽  
Parasite Isolate ◽  
Antibody Recognition ◽  
Erythrocyte Surface

ABSTRACT Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is the name given to a family of parasite proteins that are inserted into the infected erythrocyte surface. Studies using agglutination assays have shown previously that PfEMP1 epitopes are extremely diverse. In a study in Kenya, 21 parasite isolates, including nine from children with severe malaria, were tested for agglutination by 33 pairs of plasma, 21 of which were from the corresponding children. Each plasma pair consisted of a sample taken at the time of disease (acute) and one taken 3 weeks later (convalescent). In agreement with previous studies, infection was generally followed by the induction of antibodies specific to the homologous parasite isolate. In addition however, the results show that (i) some isolates were agglutinated very frequently by heterologous plasma; (ii) unexpectedly, these frequently agglutinated isolates tended to be from individuals with severe malaria; (iii) an inverse relationship existed between the agglutination frequency of each parasite isolate in heterologous plasma and the agglutinating antibody repertoire of the homologous child at the time of disease; and (iv) A 3-month-old child apparently still carrying maternal antibodies was infected by a rarely agglutinated isolate. This child’s plasma agglutinated all isolates at the time of disease, apart from the homologous isolate. These results support the idea that preexisting anti-PfEMP1 antibodies can select the variants that are expressed during a new infection and may suggest the existence of a dominant subset of PfEMP1 variants.

scholarly journals Dissecting the Gene Expression, Localization, Membrane Topology, and Function of the Plasmodium falciparum STEVOR Protein Family

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
J. Stephan Wichers ◽  
Judith A. M. Scholz ◽  
Jan Strauss ◽  
Susanne Witt ◽  
Andrés Lill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Plasma Membrane ◽  
Host Cell ◽  
Cell Invasion ◽  
Surface Antigens ◽  
Membrane Topology ◽  
Host Cell Invasion ◽  
Content Type ◽  
Variant Surface Antigens

ABSTRACT During its intraerythrocytic development, the malaria parasite Plasmodium falciparum exposes variant surface antigens (VSAs) on infected erythrocytes to establish and maintain an infection. One family of small VSAs is the polymorphic STEVOR proteins, which are marked for export to the host cell surface through their PEXEL signal peptide. Interestingly, some STEVORs have also been reported to localize to the parasite plasma membrane and apical organelles, pointing toward a putative function in host cell egress or invasion. Using deep RNA sequencing analysis, we characterized P. falciparum stevor gene expression across the intraerythrocytic development cycle, including free merozoites, in detail and used the resulting stevor expression profiles for hierarchical clustering. We found that most stevor genes show biphasic expression oscillation, with maximum expression during trophozoite stages and a second peak in late schizonts. We selected four STEVOR variants, confirmed the expected export of these proteins to the host cell membrane, and tracked them to a secondary location, either to the parasite plasma membrane or the secretory organelles of merozoites in late schizont stages. We investigated the function of a particular STEVOR that showed rhoptry localization and demonstrated its role at the parasite-host interface during host cell invasion by specific antisera and targeted gene disruption. Experimentally determined membrane topology of this STEVOR revealed a single transmembrane domain exposing the semiconserved as well as variable protein regions to the cell surface. IMPORTANCE Malaria claims about half a million lives each year. Plasmodium falciparum, the causative agent of the most severe form of the disease, uses proteins that are translocated to the surface of infected erythrocytes for immune evasion. To circumvent the detection of these gene products by the immune system, the parasite evolved a complex strategy that includes gene duplications and elaborate sequence polymorphism. STEVORs are one family of these variant surface antigens and are encoded by about 40 genes. Using deep RNA sequencing of blood-stage parasites, including free merozoites, we first established stevor expression of the cultured isolate and compared it with published transcriptomes. We reveal a biphasic expression of most stevor genes and confirm this for individual STEVORs at the protein level. The membrane topology of a rhoptry-associated variant was experimentally elucidated and linked to host cell invasion, underlining the importance of this multifunctional protein family for parasite proliferation.

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