Faculty Opinions recommendation of Breadth and magnitude of antibody responses to multiple Plasmodium falciparum merozoite antigens are associated with protection from clinical malaria.

2014 ◽  
Author(s):  
James Beeson
Keyword(s):  
Plasmodium Falciparum ◽  
Clinical Malaria ◽  
Antibody Responses ◽  
Merozoite Antigens

scholarly journals Analysis of Antibodies to Newly Described Plasmodium falciparum Merozoite Antigens Supports MSPDBL2 as a Predicted Target of Naturally Acquired Immunity

2013 ◽  
Vol 81 (10) ◽  
pp. 3835-3842 ◽  
Author(s):  
Kevin K. A. Tetteh ◽  
Faith H. A. Osier ◽  
Ali Salanti ◽  
Gathoni Kamuyu ◽  
Laura Drought ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Risk Ratio ◽  
Statistical Significance ◽  
Clinical Malaria ◽  
Content Type ◽  
Type Antigen ◽  
Falciparum Merozoite ◽  
Merozoite Antigens ◽  
Allelic Type

ABSTRACTProspective studies continue to identify malaria parasite genes with particular patterns of polymorphism which indicate they may be under immune selection, and the encoded proteins require investigation. Sixteen new recombinant protein reagents were designed to characterize three such polymorphic proteins expressed inPlasmodium falciparumschizonts and merozoites: MSPDBL1 (also termed MSP3.4) and MSPDBL2 (MSP3.8), which possess Duffy binding-like (DBL) domains, and SURFIN4.2, encoded by a member of the surface-associated interspersed (surf) multigene family. After testing the antigenicities of these reagents by murine immunization and parasite immunofluorescence, we analyzed naturally acquired antibody responses to the antigens in two cohorts in coastal Kenya in which the parasite was endemic (Chonyi [n= 497] and Ngerenya [n= 461]). As expected, the prevalence and levels of serum antibodies increased with age. We then investigated correlations with subsequent risk of clinical malaria among children <11 years of age during 6 months follow-up surveillance. Antibodies to the polymorphic central region of MSPDBL2 were associated with reduced risk of malaria in both cohorts, with statistical significance remaining for the 3D7 allelic type after adjustment for individuals' ages in years and antibody reactivity to whole-schizont extract (Chonyi, risk ratio, 0.51, and 95% confidence interval [CI], 0.28 to 0.93; Ngerenya, risk ratio, 0.38, and 95% CI, 0.18 to 0.82). For the MSPDBL1 Palo Alto allelic-type antigen, there was a protective association in one cohort (Ngerenya, risk ratio, 0.53, and 95% CI, 0.32 to 0.89), whereas the other antigens showed no protective associations after adjustment. These findings support the prediction that antibodies to the polymorphic region of MSPDBL2 contribute to protective immunity.

scholarly journals Acquired Antibodies to Merozoite Antigens in Children from Uganda with Uncomplicated or Severe Plasmodium falciparum Malaria

2013 ◽  
Vol 20 (8) ◽  
pp. 1170-1180 ◽  
Author(s):  
Hodan Ahmed Ismail ◽  
Ulf Ribacke ◽  
Linda Reiling ◽  
Johan Normark ◽  
Tom Egwang ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Uncomplicated Malaria ◽  
Severe Disease ◽  
Plasmodium Falciparum Malaria ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Content Type ◽  
Apical Membrane Antigen 1 ◽  
Merozoite Antigens ◽  
Erythrocyte Binding

ABSTRACTMalaria can present itself as an uncomplicated or severe disease. We have here studied the quantity and quality of antibody responses against merozoite antigens, as well as multiplicity of infection (MOI), in children from Uganda. We found higher levels of IgG antibodies toward erythrocyte-binding antigen EBA181, MSP2 ofPlasmodium falciparum3D7 and FC27 (MSP2-3D7/FC27), and apical membrane antigen 1 (AMA1) in patients with uncomplicated malaria by enzyme-linked immunosorbent assay (ELISA) but no differences against EBA140, EBA175, MSP1, and reticulocyte-binding protein homologues Rh2 and Rh4 or for IgM against MSP2-3D7/FC27.Patients with uncomplicated malaria were also shown to have higher antibody affinities for AMA1 by surface plasmon resonance (SPR). Decreased invasion of two clinicalP. falciparumisolates in the presence of patient plasma correlated with lower initial parasitemia in the patients, in contrast to comparisons of parasitemia to ELISA values or antibody affinities, which did not show any correlations. Analysis of the heterogeneity of the infections revealed a higher MOI in patients with uncomplicated disease, with theP. falciparumK1 MSP1 (MSP1-K1) and MSP2-3D7 being the most discriminative allelic markers. Higher MOIs also correlated positively with higher antibody levels in several of the ELISAs. In conclusion, certain antibody responses and MOIs were associated with differences between uncomplicated and severe malaria. When different assays were combined, some antibodies, like those against AMA1, seemed particularly discriminative. However, only decreased invasion correlated with initial parasitemia in the patient, signaling the importance of functional assays in understanding development of immunity against malaria and in evaluating vaccine candidates.

scholarly journals Cytophilic Immunoglobulin Responses to Plasmodium falciparum Glutamate-Rich Protein Are Correlated with Protection against Clinical Malaria in Dielmo, Senegal

2000 ◽  
Vol 68 (5) ◽  
pp. 2617-2620 ◽  
Author(s):  
Claude Oeuvray ◽  
Michael Theisen ◽  
Christophe Rogier ◽  
Jean-Francois Trape ◽  
Søren Jepsen ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Protective Immunity ◽  
Clinical Malaria ◽  
Parasite Growth ◽  
Antibody Responses ◽  
Plasma Samples ◽  
Confounding Effect ◽  
Human Antibodies ◽  
Age Related ◽  
Effect Of Age

ABSTRACT The goal of this study was to analyze antibody responses toPlasmodium falciparum glutamate-rich protein (GLURP) using clinical data and plasma samples obtained from villagers of Dielmo, Senegal. This molecule was chosen because it is targeted by human antibodies which induce parasite growth inhibition in antibody-dependent cellular inhibition (ADCI) assays. The results showed a strong correlation between protection against malaria attacks and levels of immunoglobulin G2 (IgG2) and IgG3 against GLURP94–489 (R0) and IgG3 against GLURP705–1178 (R2) when corrected for the confounding effect of age-related exposure to malaria. Thus, GLURP may play a role in the induction of protective immunity against P. falciparum malaria.

scholarly journals Allele Specificity of Naturally Acquired Antibody Responses against Plasmodium falciparum Apical Membrane Antigen 1

2005 ◽  
Vol 73 (1) ◽  
pp. 422-430 ◽  
Author(s):  
Alfred Cortés ◽  
Mata Mellombo ◽  
Rosella Masciantonio ◽  
Vince J. Murphy ◽  
John C. Reeder ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Apical Membrane ◽  
Age Groups ◽  
Antibody Responses ◽  
Allelic Form ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Younger Age ◽  
Merozoite Antigens ◽  
Allele Specificity

ABSTRACT Antibody responses against proteins located on the surface or in the apical organelles of merozoites are presumed to be important components of naturally acquired protective immune responses against the malaria parasite Plasmodium falciparum. However, many merozoite antigens are highly polymorphic, and antibodies induced against one particular allelic form might not be effective in controlling growth of parasites expressing alternative forms. The apical membrane antigen 1 (AMA1) is a polymorphic merozoite protein that is a target of naturally acquired invasion-inhibitory antibodies and is a leading asexual-stage vaccine candidate. We characterized the antibody responses against AMA1 in 262 individuals from Papua New Guinea exposed to malaria by using different allelic forms of the full AMA1 ectodomain and some individual subdomains. The majority of individuals had very high levels of antibodies against AMA1. The prevalence and titer of these antibodies increased with age. Although antibodies against conserved regions of the molecule were predominant in the majority of individuals, most plasma samples also contained antibodies directed against polymorphic regions of the antigen. In a few individuals, predominantly from younger age groups, the majority of antibodies against AMA1 were directed against polymorphic epitopes. The D10 allelic form of AMA1 apparently contains most if not all of the epitopes present in the other allelic forms tested, which might argue for its inclusion in future AMA1-based vaccines to be tested. Some important epitopes in AMA1 involved residues located in domain II or III but depended on more than one domain.

scholarly journals Breadth of Anti-Merozoite Antibody Responses Is Associated With the Genetic Diversity of Asymptomatic Plasmodium falciparum Infections and Protection Against Clinical Malaria

2013 ◽  
Vol 57 (10) ◽  
pp. 1409-1416 ◽  
Author(s):  
Josea Rono ◽  
Faith H. A. Osier ◽  
Daniel Olsson ◽  
Scott Montgomery ◽  
Leah Mhoja ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Clinical Malaria ◽  
Antibody Responses

scholarly journals Immunoglobulin G Antibodies to Merozoite Surface Antigens Are Associated with Recovery from Chloroquine-Resistant Plasmodium falciparum in Gambian Children

2006 ◽  
Vol 74 (5) ◽  
pp. 2887-2893 ◽  
Author(s):  
Margaret Pinder ◽  
Colin J. Sutherland ◽  
Fatoumatta Sisay-Joof ◽  
Jamila Ismaili ◽  
Matthew B. B. McCall ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immunoglobulin G ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Clinical Malaria ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasma Samples ◽  
Apical Membrane Antigen 1 ◽  
Merozoite Antigens ◽  
Functional Immunity

ABSTRACT We examined the hypothesis that recovery from uncomplicated malaria in patients carrying drug-resistant Plasmodium falciparum is a measure of acquired functional immunity and may therefore be associated with humoral responses to candidate vaccine antigens. Gambian children with malaria were treated with chloroquine in 28-day trials, and recovery was defined primarily as the absence of severe clinical malaria at any time and absence of parasitemia with fever after 3 days. Plasma samples from these children were assayed by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) to recombinant merozoite antigens: apical membrane antigen 1 (AMA-1) and the 19-kDa C-terminal region of merozoite surface protein 1 (MSP-119), including antigenic variants of MSP-119 with double and triple substitutions. Antigen-specific IgG was more frequent in children who recovered, particularly that for MSP-119 (age-adjusted odds ratios: 0.32 [95% confidence interval, 0.05, 1.87; P = 0.168] for AMA-1, 0.19 [0.03, 1.11; P = 0.019] for recombinant MSP-119, 0.24 [0.04, 1.31; P = 0.032] for the recombinant MSP-119 double variant, and 0.18 [0.03, 0.97; P = 0.013] for the triple variant). IgG titers to MSP-119 and to the triple variant were higher in plasma samples taken 7 days after chloroquine treatment from children who carried resistant parasites but recovered and remained parasite free. Moreover, in children who were parasitemic on day 14 or day 28, there was an age-independent relationship between parasite density and IgG to both MSP-119 and the triple variant (coefficients of −0.550 and −0.590 and P values of 0.002 and 0.001, respectively). The results validate the use of this approach to identify antigens that are associated with protection from malaria.

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