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Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein and Clinical Immunity to Malaria in Rural Amazonians.

ABSTRACT: Antibodies to the cysteine-rich domain II of Plasmodium vivax Duffy binding protein (PvDBP) can inhibit binding of this parasite ligand to its receptor on red blood cells, the Duffy antigen/receptor for chemokines. These binding-inhibitory antibodies (BIAbs) also inhibit P. vivax invasion of reticulocytes in vitro.To investigate whether naturally acquired anti-PvDBP antibodies are associated with reduced risk of clinical malaria in a population exposed to low levels of P. vivax transmission, we measured total levels of immunoglobulin G antibodies to 5 PvDBP variants and used a functional in vitro assay to quantify their binding-inhibitory activity in a cohort of 466 rural Amazonians followed up for up to 37 months.No association between total immunoglobulin G antibody responses to any PvDBP variant and risk of symptomatic, laboratory-confirmed vivax malaria was observed in this cohort. However, a Cox proportional hazards model, adjusted for age, sex, and genotype for the Duffy antigen/receptor for chemokines, showed a >40% decrease in the prospective risk of clinical vivax malaria in subjects with the strongest BIAb responses (upper and middle terciles). High BIAb responses were mostly PvDBP variant transcending and stable over time.Strong naturally acquired BIAb responses are associated with a reduced risk of clinical P. vivax malaria in rural Amazonians.

SUBMITTER: Nicolete VC

PROVIDER: S-EPMC5091372 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein and Clinical Immunity to Malaria in Rural Amazonians.

Nicolete Vanessa C VC Frischmann Sarah S Barbosa Susana S King Christopher L CL Ferreira Marcelo U MU

The Journal of infectious diseases 20160830 10

<h4>Background</h4>Antibodies to the cysteine-rich domain II of Plasmodium vivax Duffy binding protein (PvDBP) can inhibit binding of this parasite ligand to its receptor on red blood cells, the Duffy antigen/receptor for chemokines. These binding-inhibitory antibodies (BIAbs) also inhibit P. vivax invasion of reticulocytes in vitro.<h4>Methods</h4>To investigate whether naturally acquired anti-PvDBP antibodies are associated with reduced risk of clinical malaria in a population exposed to low l ...[more]

PMID: 27578850

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Project description:A vaccine to eliminate malaria would need a multi-stage and multi-species composition to achieve robust protection, but the lack of knowledge about antigen targets and mechanisms of protection precludes the development of fully efficacious malaria vaccines, especially for Plasmodium vivax (Pv). Pregnant women constitute a risk population who would greatly benefit from a vaccine preventing the adverse events of Plasmodium infection during gestation. We hypothesized that functional immune responses against putative targets of naturally acquired immunity to malaria and vaccine candidates will be associated with protection against malaria infection and/or poor outcomes during pregnancy. We measured (i) IgG responses to a large panel of Pv and Plasmodium falciparum (Pf) antigens, (ii) the capacity of anti-Pv ligand Duffy binding protein (PvDBP) antibodies to inhibit binding to Duffy antigen, and (iii) cellular immune responses to two Pv antigens, in a subset of 1,056 pregnant women from Brazil, Colombia, Guatemala, India, and Papua New Guinea (PNG). There were significant intraspecies and interspecies correlations for most antibody responses (e.g., PfMSP119 versus PfAMA1, Spearman's rho = 0.81). Women from PNG and Colombia had the highest levels of IgG overall. Submicroscopic infections seemed sufficient to boost antibody responses in Guatemala but not antigen-specific cellular responses in PNG. Brazil had the highest percentage of Duffy binding inhibition (p-values versus Colombia: 0.040; Guatemala: 0.047; India: 0.003, and PNG: 0.153) despite having low anti-PvDBP IgG levels. Almost all antibodies had a positive association with present infection, and coinfection with the other species increased this association. Anti-PvDBP, anti-PfMSP1, and anti-PfAMA1 IgG levels at recruitment were positively associated with infection at delivery (p-values: 0.010, 0.003, and 0.023, respectively), suggesting that they are markers of malaria exposure. Peripheral blood mononuclear cells from Pv-infected women presented fewer CD8+IFN-γ+ T cells and secreted more G-CSF and IL-4 independently of the stimulus used in vitro. Functional anti-PvDBP levels at recruitment had a positive association with birth weight (difference per doubling antibody levels: 45 g, p-value: 0.046). Thus, naturally acquired binding-inhibitory antibodies to PvDBP might confer protection against poor outcomes of Pv malaria in pregnancy.

Dataset Information

Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein and Clinical Immunity to Malaria in Rural Amazonians.

Publications

Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein and Clinical Immunity to Malaria in Rural Amazonians.

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