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Antibody responses and avidity of naturally acquired anti-Plasmodium vivax Duffy binding protein (PvDBP) antibodies in individuals from an area with unstable malaria transmission.

ABSTRACT: Plasmodium vivax remains an important cause of morbidity outside Africa, and no effective vaccine is available against this parasite. The P. vivax Duffy binding protein (PvDBP) is essential during merozoite invasion into erythrocytes, and it is a target for protective immunity against malaria. This investigation was designed to evaluate naturally acquired antibodies to two variant forms of PvDBP-II antigen (DBP-I and -VI) in malaria individuals (N = 85; median = 22 years) who were living in hypoendemic areas in Iran. The two PvDBP-II variants were expressed in Escherichia coli, and immunoglobulin G (IgG) isotype composition and avidity of naturally acquired antibodies to these antigens were measured using enzyme-linked immunosorbent assay (ELISA). Results showed that almost 32% of the studied individuals had positive antibody responses to the two PvDBP-II variants, and the prevalence of responders did not differ significantly (P > 0.05; ?(2) test). The IgG-positive samples exhibited 37.03% and 40.8% high-avidity antibodies for PvDBP-I and PvDBP-VI variants, respectively. Furthermore, high-avidity IgG1 antibody was found in 39.1% of positive sera for each examined variant antigen. The avidity of antibodies for both PvDBP variant antigens and the prevalence of responders with high- and intermediate-avidity IgG, IgG1, and IgG3 antibodies were similar in patients (P > 0.05; ?(2) test). Moreover, the prevalence of IgG antibody responses to the two variants significantly increased with exposure and host age. To sum up, the results provided additional data in our understanding of blood-stage immunity to PvDBP, supporting the rational development of an effective blood-stage vaccine based on this antigen.

SUBMITTER: Zakeri S

PROVIDER: S-EPMC3110374 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Antibody responses and avidity of naturally acquired anti-Plasmodium vivax Duffy binding protein (PvDBP) antibodies in individuals from an area with unstable malaria transmission.

Zakeri Sedigheh S Babaeekhou Laleh L Mehrizi Akram Abouie AA Abbasi Maryam M Djadid Navid Dinparast ND

The American journal of tropical medicine and hygiene 20110601 6

Plasmodium vivax remains an important cause of morbidity outside Africa, and no effective vaccine is available against this parasite. The P. vivax Duffy binding protein (PvDBP) is essential during merozoite invasion into erythrocytes, and it is a target for protective immunity against malaria. This investigation was designed to evaluate naturally acquired antibodies to two variant forms of PvDBP-II antigen (DBP-I and -VI) in malaria individuals (N = 85; median = 22 years) who were living in hypo ...[more]

PMID: 21633032

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Project description:Understanding naturally acquired immunity to infections caused by Plasmodia in different malaria endemicity settings is needed for better vaccine designs and for exploring antibody responses as a proxy marker of malaria transmission intensity. This study investigated the sero-epidemiology of malaria along the international border between China and Myanmar, where malaria elimination action plans are in place. This study recruited 233 P. vivax and 156 P. falciparum infected subjects with acute malaria at the malaria clinics and hospitals. In addition, 93 and 67 healthy individuals from the same endemic region or from non-endemic region, respectively, were used as controls. Acute malaria infections were identified by microscopy. Anti-recombinant PfMSP119 and PvMSP119 antibody levels were measured by ELISA. Antibody responses to respective MSP119 were detected in 50.9% and 78.2% patients with acute P. vivax and P. falciparum infections, respectively. There were cross-reacting antibodies in Plasmodium patients against these two recombinant proteins, though we could not exclude the possibility of submicroscopic mixed-species infections. IgG1, IgG3 and IgG4 were the major subclasses. Interestingly, 43.2% of the healthy endemic population also had antibodies against PfMSP119, whereas only 3.9% of this population had antibodies against PvMSP119. Higher antibody levels were correlated with age and parasite density, but not with season, gender or malaria history. Both total IgG and individual IgG subclasses underwent substantial declines during the convalescent period in three months. This study demonstrated that individuals in a hypoendemic area with coexistence of P. vivax and P. falciparum can mount rapid antibody responses against both PfMSP119 and PvMSP119. The significantly higher proportion of responders to PfMSP119 in the healthy endemic population indicates higher prevalence of P. falciparum in the recent past. Specific antibodies against PvMSP119 could serve as a marker of recent exposure to P. vivax in epidemiological studies.

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

Antibody responses and avidity of naturally acquired anti-Plasmodium vivax Duffy binding protein (PvDBP) antibodies in individuals from an area with unstable malaria transmission.

Publications

Antibody responses and avidity of naturally acquired anti-Plasmodium vivax Duffy binding protein (PvDBP) antibodies in individuals from an area with unstable malaria transmission.

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