scholarly journals Expression of Variant Surface Antigens by Plasmodium falciparum Parasites in the Peripheral Blood of Clinically Immune Pregnant Women Indicates Ongoing Placental Infection

2003 ◽  
Vol 71 (3) ◽  
pp. 1584-1586 ◽  
Author(s):  
Michael F. Ofori ◽  
Trine Staalsoe ◽  
Victoria Bam ◽  
Maja Lundquist ◽  
Kim P. David ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Pregnant Women ◽  
Peripheral Blood ◽  
Surface Antigens ◽  
Vaccine Research ◽  
Variant Surface Antigens ◽  
Placental Infection

ABSTRACT Placenta-sequestered Plasmodium falciparum parasites that cause pregnancy-associated malaria (PAM) in otherwise clinically immune women express distinct variant surface antigens (VSAPAM) not expressed by parasites in nonpregnant individuals. We report here that parasites from the peripheral blood of clinically immune pregnant women also express VSAPAM, making them a convenient source of VSAPAM expressors for PAM vaccine research.

scholarly journals Parity and Placental Infection Affect Antibody Responses againstPlasmodium falciparumduring Pregnancy

2011 ◽  
Vol 79 (4) ◽  
pp. 1654-1659 ◽  
Author(s):  
Alfredo Mayor ◽  
Eduard Rovira-Vallbona ◽  
Sonia Machevo ◽  
Quique Bassat ◽  
Ruth Aguilar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Pregnant Women ◽  
Peripheral Blood ◽  
Surface Antigens ◽  
Antibody Responses ◽  
Bed Nets ◽  
Variant Surface Antigens ◽  
Placental Infection ◽  
Merozoite Antigens ◽  
Antibody Levels

ABSTRACTWomen are at higher risk ofPlasmodium falciparuminfection when pregnant. The decreasing risk of malaria with subsequent pregnancies is attributed to parity-dependent acquisition of antibodies against placental parasites expressing variant surface antigens, VAR2CSA, that mediate placental sequestration through adhesion to chondroitin sulfate A (CSA). However, modulation of immunity during pregnancy may also contribute to increase the risk of malaria. We compared antibody responses among 30 Mozambican primigravidae and 60 multigravidae at delivery, 40 men, and 40 children. IgG levels were measured against the surface antigens of erythrocytes infected withP. falciparumisolated from 12 pregnant women (4 placental and 8 peripheral blood isolates) and 26 nonpregnant hosts. We also measured IgG levels against merozoite recombinant antigens and total IgG. PlacentalP. falciparuminfection was associated with increased levels of total IgG as well as IgG levels against merozoite antigens and parasite isolates from pregnant and nonpregnant hosts. We therefore stratified comparisons of antibody levels by placental infection. Compared to multigravidae, uninfected primigravidae had lower total IgG as well as lower levels of IgGs against peripheral blood isolates from both pregnant and nonpregnant hosts. These differences were not explained by use of bed nets, season at delivery, neighborhood of residence, or age. Compared to men, infected primigravidae had higher levels of IgGs against isolates from pregnant women and CSA-binding lines but not against other isolates, supporting the concept of a pregnancy-specific development of immunity to these parasite variants. Results of this study show that parity and placental infection can modulate immune responses during pregnancy against malaria parasites.

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 VAR2CSA and protective immunity against pregnancy-associated Plasmodium falciparum malaria

Parasitology ◽  
2007 ◽  
Vol 134 (13) ◽  
pp. 1871-1876 ◽  
Author(s):  
L. HVIID ◽  
A. SALANTI
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
Pregnant Women ◽  
Protective Immunity ◽  
Plasmodium Falciparum Malaria ◽  
Surface Antigens ◽  
Variant Surface Antigens ◽  
Important Target ◽  
First Time ◽  
Stable Transmission

SUMMARYPeople living in areas with stable transmission of P. falciparum parasites acquire protective immunity to malaria over a number of years and following multiple disease episodes. Immunity acquired this way is mediated by IgG with specificity for parasite-encoded, clonally variant surface antigens (VSA) on the surface of infected erythrocytes (IEs). However, women in endemic areas become susceptible to P. falciparum infection when they become pregnant, particularly for the first time, regardless of previously acquired protective immunity. This conundrum was resolved when it was observed that the selective placental accumulation of IEs that characterizes pregnancy-associated malaria (PAM) is caused by an immunologically and functionally unique subset of VSA (VSAPAM) that is only expressed by parasites infecting pregnant women, and that protective immunity to PAM is mediated by IgG with specificity for VSAPAM. In this review we summarize the research leading to the identification of the distinctly structured PfEMP1 variant VAR2CSA as the dominant PAM-type VSA and as the clinically most important target of the protective immune response to placental P. falciparum infection.

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 Relationship between Human Immunodeficiency Virus Type 1 Coinfection, Anemia, and Levels and Function of Antibodies to Variant Surface Antigens in Pregnancy-Associated Malaria

2009 ◽  
Vol 16 (3) ◽  
pp. 312-319 ◽  
Author(s):  
Anthony Jaworowski ◽  
Liselle A. Fernandes ◽  
Francisca Yosaatmadja ◽  
Gaoqian Feng ◽  
Victor Mwapasa ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Pregnant Women ◽  
Surface Antigens ◽  
Opsonic Activity ◽  
Variant Surface Antigens ◽  
Immunodeficiency Virus ◽  
Blocking Activity ◽  
Hiv 1 ◽  
In Pregnancy

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) coinfection decreases antibodies to variant surface antigens implicated in pregnancy-associated malaria (VSA-PAM) caused by Plasmodium falciparum. The effect of HIV-1 on antibody functions that may protect mothers from pregnancy-associated malaria is unknown. Sera from multigravid pregnant women with malaria and HIV-1 coinfection (n = 58) or malaria alone (n = 29) and from HIV-1-infected (n = 102) or -uninfected (n = 54) multigravidae without malaria were analyzed for anti-VSA-PAM antibodies by flow cytometry, the ability to inhibit adhesion to chondroitin sulfate A, or to opsonize CS2-infected erythrocytes for phagocytosis by THP-1 cells. In women with malaria, anti-VSA-PAM levels correlated better with opsonic activity (r = 0.60) than with adhesion-blocking activity (r = 0.33). In univariate analysis, HIV-1 coinfection was associated with lower opsonic activity but not adhesion-blocking activity or anti-VSA-PAM levels. Malaria-infected women with anemia (hemoglobin levels of <11.0 g/dl) had lower opsonic activity than nonanemic women (P = 0.007) independent of HIV-1 status. By multivariate analysis, in malaria-infected women, anemia (but not HIV status) was associated with opsonic activity. In women without malaria, opsonic activity was not associated with either anemia or HIV-1 status. In multigravid pregnant women with malaria, impaired serum opsonic activity may contribute to anemia and possibly to the decreased immunity to pregnancy-associated malaria associated with HIV-1.

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.

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