Immunoglobulin G Subclass-Specific Responses against
            <i>Plasmodium falciparum</i>
            Merozoite Antigens Are Associated with Control of Parasitemia and Protection from Symptomatic Illness

Stanisic, Danielle I.; Richards, Jack S.; McCallum, Fiona; Michon, P; King, Christopher L.; Schoepflin, Sonja; Gilson, Paul R.; Murphy, Vincent J.; Anders, Robin F.; Müeller, Ivo; Beeson, James G.

doi:10.1128/iai.01129-08

Cited by 240 publications

(315 citation statements)

References 48 publications

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“…The genetic diversity of a parasite population is shaped by various influences, including genetic drift, mutation, natural selection, and gene flow. 40 MSP2 is the second most abundant protein on the surface of the merozoite 41 and a target of naturally acquired antibodies, 42,43 and therefore diversity is influenced by immune (balancing) selection. A comparison of msp2 diversity between Tanzania and PNG showed many more alleles (A = 76 and 35, respectively), however only slightly higher expected heterozygosity (H e = 0.933 and 0.965, respectively) in the African population where transmission is approximately ten times that of PNG.…”

Section: Discussionmentioning

confidence: 99%

High Levels of Genetic Diversity of Plasmodium falciparum Populations in Papua New Guinea despite Variable Infection Prevalence

Barry

Schultz

Senn

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. High levels of genetic diversity in Plasmodium falciparum populations are an obstacle to malaria control. Here, we investigate the relationship between local variation in malaria epidemiology and parasite genetic diversity in Papua New Guinea (PNG). Cross-sectional malaria surveys were performed in 14 villages spanning four distinct malariaendemic areas on the north coast, including one area that was sampled during the dry season. High-resolution msp2 genotyping of 2,147 blood samples identified 761 P. falciparum infections containing a total of 1,392 clones whose genotypes were used to measure genetic diversity. Considerable variability in infection prevalence and mean multiplicity of infection was observed at all of the study sites, with the area sampled during the dry season showing particularly striking local variability. Genetic diversity was strongly associated with multiplicity of infection but not with infection prevalence. In highly endemic areas, differences in infection prevalence may not translate into a decrease in parasite population diversity.

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Section: Discussionmentioning

confidence: 99%

High Levels of Genetic Diversity of Plasmodium falciparum Populations in Papua New Guinea despite Variable Infection Prevalence

Barry

Schultz

Senn

et al. 2013

The American Society of Tropical Medicine and Hygiene

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“…Abs to recombinant proteins were measured by ELISAs using established methods (13,35). Briefly, Ags were coated onto Maxisorp microtiter plates (Nunc, Roskilde, Denmark) at 1-2 mg/ml (schizont lysate at 4.6 mg/ml).…”

Section: Elisamentioning

confidence: 99%

Evidence That the Erythrocyte Invasion Ligand PfRh2 is a Target of Protective Immunity against Plasmodium falciparum Malaria

Reiling

Richards

Fowkes

et al. 2010

The Journal of Immunology

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Abs targeting blood-stage Ags of Plasmodium falciparum are important in acquired immunity to malaria, but major targets remain unclear. The P. falciparum reticulocyte-binding homologs (PfRh) are key ligands used by merozoites during invasion of erythrocytes. PfRh2a and PfRh2b are functionally important members of this family and may be targets of protective immunity, but their potential role in human immunity has not been examined. We expressed eight recombinant proteins covering the entire PfRh2 common region, as well as PfRh2a- and PfRh2b-specific regions. Abs were measured among a cohort of 206 Papua New Guinean children who were followed prospectively for 6 mo for reinfection and malaria. At baseline, Abs were associated with increasing age and active infection. High levels of IgG to all PfRh2 protein constructs were strongly associated with protection from symptomatic malaria and high-density parasitemia. The predominant IgG subclasses were IgG1 and IgG3, with little IgG2 and IgG4 detected. To further understand the significance of PfRh2 as an immune target, we analyzed PfRh2 sequences and found that polymorphisms are concentrated in an N-terminal region of the protein and seem to be under diversifying selection, suggesting immune pressure. Cluster analysis arranged the sequences into two main groups, suggesting that many of the haplotypes identified may be antigenically similar. These findings provide evidence suggesting that PfRh2 is an important target of protective immunity in humans and that Abs act by controlling blood-stage parasitemia and support its potential for vaccine development.

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“…During the fi rst months of life, maternal antibodies may mediate partial protection against P. falciparum infection [4,5], while naturally acquired protective immunity against malaria is slow to develop, remains incomplete, and requires repeated exposure to infection which will generate memory B cells, which produce specifi c IgG subclasses able to neutralize the blood developmental stages of the parasite [6][7][8][9][10]. The secretion of cytokines and chemokines by T cells, monocytes, and NK cells is another essential prerequisite for the regulation of cellular effector mechanisms against P. falciparum blood-stage parasites [11], but infl ammatory cytokines and chemokines may also exacerbate disease manifestation and organ-specifi c pathogenesis [12].…”

Section: Introductionmentioning

confidence: 99%

Chemokine levels and parasite- and allergen-specific antibody responses in children and adults with severe or uncomplicatedPlasmodium falciparummalaria

Wangala¹,

Vovor²,

Gantin³

et al. 2015

European Journal of Microbiology and Immunology

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Chemokine a nd antibody response profiles were investigated in children and adults with severe or uncomplicated Plasmodium falciparum malaria; the aim was to reveal which profiles are associated with severe disease, as often seen in nonimmune children, or with mild and uncomplicated disease, as seen in semi-immune adults. Blood samples were obtained from children under 5 years of age as well as adults with falciparum malaria. Classification of malaria was performed according to parasite densities and hemoglobin concentrations. Plasma levels of chemokines (IL-8, IP-10, MCP-4, TARC, PARC, MIP-1δ, eotaxins) were quantified, and antibody responses (IgE, IgG1, and IgG4) to P. falciparum, Entamoeba histolytica-specific antigen, and mite allergen extracts were determined. In children with severe malaria proinflammatory, IL-8, IP10, MIP-1δ, and LARC were at highly elevated levels, suggesting an association with severe disease. In contrast, the Th2-type chemokines TARC, PARC, and eotaxin-2 attained in children the same levels as in adults suggesting the evolution of immune regulatory components. In children with severe malaria, an elevated IgG1 and IgE reactivity to mite allergens and intestinal protozoan parasites was observed. In conclusion, exacerbated proinflammatory chemokines together with IgE responses to mite allergens or E. histolytica-specific antigen extract were observed in children with severe falciparum malaria.

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Immunoglobulin G Subclass-Specific Responses against Plasmodium falciparum Merozoite Antigens Are Associated with Control of Parasitemia and Protection from Symptomatic Illness

Abstract: Substantial evidence indicates that antibodies to

Cited by 240 publications

References 48 publications

High Levels of Genetic Diversity of Plasmodium falciparum Populations in Papua New Guinea despite Variable Infection Prevalence

High Levels of Genetic Diversity of Plasmodium falciparum Populations in Papua New Guinea despite Variable Infection Prevalence

Evidence That the Erythrocyte Invasion Ligand PfRh2 is a Target of Protective Immunity against Plasmodium falciparum Malaria

Chemokine levels and parasite- and allergen-specific antibody responses in children and adults with severe or uncomplicatedPlasmodium falciparummalaria

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