scholarly journals Geographical and Temporal Conservation of Antibody Recognition of Plasmodium falciparum Variant Surface Antigens

2004 ◽  
Vol 72 (6) ◽  
pp. 3531-3535 ◽  
Author(s):  
Morten A. Nielsen ◽  
Lasse S. Vestergaard ◽  
John Lusingu ◽  
Jørgen A. L. Kurtzhals ◽  
Haider A. Giha ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Protective Immunity ◽  
Surface Antigens ◽  
African Countries ◽  
Variant Surface Antigens ◽  
Antibody Recognition ◽  
Specific Immunoglobulin ◽  
Life Threatening ◽  
Specific Igg ◽  
Plasma Collection

ABSTRACT The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSASM) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSASM-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSASM, is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparum malaria.

scholarly journals Intermittent Preventive Sulfadoxine-Pyrimethamine Treatment of Primigravidae Reduces Levels of Plasma Immunoglobulin G, Which Protects against Pregnancy-Associated Plasmodium falciparum Malaria

2004 ◽  
Vol 72 (9) ◽  
pp. 5027-5030 ◽  
Author(s):  
Trine Staalsoe ◽  
Caroline E Shulman ◽  
Edgar K. Dorman ◽  
Ken Kawuondo ◽  
Kevin Marsh ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immunoglobulin G ◽  
Protective Immunity ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Plasmodium Falciparum Malaria ◽  
World Health ◽  
Variant Surface Antigens ◽  
Specific Igg ◽  
Health Organization

ABSTRACT Pregnancy-associated malaria (PAM) is an important cause of maternal and neonatal suffering. It is caused by Plasmodium falciparum capable of inhabiting the placenta through expression of particular variant surface antigens (VSA) with affinity for proteoglycans such as chondroitin sulfate A. Protective immunity to PAM develops following exposure to parasites inhabiting the placenta, and primigravidae are therefore particularly susceptible to PAM. The adverse consequences of PAM in primigravidae are preventable by intermittent preventive treatment (IPTp), where women are given antimalarials at specified intervals during pregnancy, but this may interfere with acquisition of protective PAM immunity. We found that Kenyan primigravidae receiving sulfadoxine-pyrimethamine IPTp had significantly lower levels of immunoglobulin G (IgG) with specificity for the type of parasite-encoded VSA—called VSAPAM—that specifically mediate protection against PAM than did women receiving a placebo. VSAPAM-specific IgG levels depended on the number of IPTp doses received and were sufficiently low to be of clinical concern among multidose recipients. Our data suggest that IPTp should be extended to women of all parities, in line with current World Health Organization recommendations.

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.

The use of cryopreserved mature trophozoites in assessing antibody recognition of variant surface antigens of Plasmodium falciparum-infected erythrocytes

2004 ◽  
Vol 288 (1-2) ◽  
pp. 9-18 ◽  
Author(s):  
Samson M Kinyanjui ◽  
Tevis Howard ◽  
Thomas N Williams ◽  
Peter C Bull ◽  
Christopher I Newbold ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Antigens ◽  
Variant Surface Antigens ◽  
Antibody Recognition

scholarly journals Malaria-Induced Acquisition of Antibodies to Plasmodium falciparum Variant Surface Antigens

2002 ◽  
Vol 70 (6) ◽  
pp. 2982-2988 ◽  
Author(s):  
Michael F. Ofori ◽  
Daniel Dodoo ◽  
Trine Staalsoe ◽  
Jørgen A. L. Kurtzhals ◽  
Kwadwo Koram ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Protective Immunity ◽  
Surface Antigens ◽  
Specific Antibodies ◽  
Variant Surface Antigens ◽  
Detailed Kinetics ◽  
Antibody Levels ◽  
Kinetics Of ◽  
Malaria Episodes ◽  
Sustained Increase

ABSTRACT In areas of intense Plasmodium falciparum transmission, protective immunity is acquired during childhood in parallel with acquisition of agglutinating antibodies to parasite-encoded variant surface antigens (VSA) expressed on parasitized red blood cells. In a semi-immune child in such an area, clinical disease is caused mainly by parasites expressing VSA not recognized by preexisting VSA-specific antibodies in that child. Such malaria episodes are known to cause an increase in agglutinating antibodies specifically recognizing VSA expressed by the parasite isolate causing the illness, whereas antibody responses to other parasite isolates are relatively unaffected. However, the detailed kinetics of this VSA antibody acquisition are unknown and hence were the aim of this study. We show that P. falciparum malaria in Ghanaian children generally caused a rapid and sustained increase in variant-specific VSA antibody levels, while more transient and limited increases in levels of antibodies to VSA expressed by other parasite isolates were also seen. Plasma VSA antibody levels were positively correlated with the age of the healthy plasma donors but negatively correlated with the age of the parasite donors (the malaria patient). The data from this first detailed longitudinal study of acquisition of VSA antibodies support the hypothesis that naturally acquired protective immunity to P. falciparum malaria is mediated, at least in part, by VSA-specific antibodies.

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.

Sign in / Sign up

Export Citation Format

Share Document