Naturally Acquired Binding-Inhibitory Antibodies to<i>Plasmodium vivax</i>Duffy Binding Protein and Clinical Immunity to Malaria in Rural Amazonians

Nicolete, Vanessa C; Frischmann, Sarah; Barbosa, Susana; King, Christopher L.; Ferreira, Marcelo U.

doi:10.1093/infdis/jiw407

Cited by 45 publications

(74 citation statements)

References 28 publications

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“…Using a recombinant DBPII (rDBPII)-red blood cell binding assay, we screened the plasma of 267 individuals infected with blood-stage Pv, of which 151 (57%) were infected by single copy parasites and 116 (43%) by parasites with multiple pvdbp copies. As expected, because BIAbs are both rarely acquired under natural exposure and protective against Pv malaria 16,20 , only 8 individuals had BIAbs highly inhibiting rDBPII-red blood cell binding ( > 90% inhibition at 1:5 plasma dilution) (Fig. 5a).…”

Section: Resultssupporting

confidence: 72%

“…While there is significant polymorphism in DBPII, the binding residues are conserved [9][10][11][12][13][14][15] . Although individuals residing in Pv endemic areas commonly have antibodies to DBPII non-binding immuno-dominant residues, only a minority of patients can develop antibodies targeting binding amino acids of the protein resulting in strain-transcending naturally acquired immunity against Pv [16][17][18][19][20] . Yet some individuals with high titers of these naturally acquired antibodies remain susceptible to malaria infection and disease suggesting alternative mechanisms to antigenic diversity that the parasite might have evolved to escape this strain-transcending immunity.…”

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confidence: 99%

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Amplification of Duffy binding protein-encoding gene allows Plasmodium vivax to evade host anti-DBP humoral immunity

et al. 2020

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Antigenic variation, the capacity to produce a range of variable antigens, is a well-described strategy of Plasmodium and other parasites to evade host immunity. Here, we show that gene amplification is an additional evasion mechanism used by Plasmodium vivax to escape humoral immunity targeting PvDBP, the key ligand involved in reticulocyte invasion. PvDBP gene amplification leads to increased mRNA levels and protects P. vivax in vitro against invasion inhibitory human monoclonal antibodies targeting a conserved binding domain of DBP. Patient samples suggest that parasites with increased pvdbp copy number are able to infect individuals with naturally acquired antibodies highly blocking the binding of PvDBP to the Duffy receptor. These results show that gene copy number variation affect the parasite's ability to evade anti-PvDBP humoral immunity.

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Section: Resultssupporting

confidence: 72%

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confidence: 99%

Amplification of Duffy binding protein-encoding gene allows Plasmodium vivax to evade host anti-DBP humoral immunity

et al. 2020

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“…Interestingly, clinical immunity against P vivax appears to develop faster than that to P falciparum in communities where both malaria parasites co‐exist . Significantly, high expression of naturally acquired antibodies against surface antigens of selected asexual blood stages of P vivax has been associated with reduced prospective risk of vivax malaria attacks in Amazonian cohorts …”

Section: Introductionmentioning

confidence: 99%

“…5,6 Significantly, high expression of naturally acquired antibodies against surface antigens of selected asexual blood stages of P vivax has been associated with reduced prospective risk of vivax malaria attacks in Amazonian cohorts. 7,8 Once acquired, the clinical immunity against malaria requires persistent or frequent boosting and may wane when subjects move away from communities with high incidence of malaria and remain unexposed for years. 9 Levels of circulating P falciparum-specific antibodies decline rapidly in unexposed subjects, which was consistent with previous reports of defective B-cell memory in malaria.…”

Section: Introductionmentioning

confidence: 99%

Apical membrane protein 1‐specific antibody profile and temporal changes in peripheral blood B‐cell populations in Plasmodium vivax malaria

Soares

Cunha

Ferraz-Nogueira

et al. 2019

Parasite Immunology

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Plasmodium falciparum‐specific antibodies tend to be short‐lived, but their cognate memory B cells (MBCs) circulate in the peripheral blood of exposed subjects for several months or years after the last infection. However, the time course of antigen‐specific antibodies and B‐cell responses to the relatively neglected parasite Plasmodium vivax remains largely unexplored. Here, we showed that uncomplicated vivax malaria elicits short‐lived antibodies but long‐lived MBC responses to a major blood‐stage P vivax antigen, apical membrane protein 1 (PvAMA‐1), in subjects exposed to declining malaria transmission in the Amazon Basin of Brazil. We found that atypical (CD19+CD10−CD21−CD27−) MBCs, which appear to share a common precursor with classical MBCs but are unable to differentiate into antibody‐secreting cells, significantly outnumbered classical MBCs by 5:1 in the peripheral blood of adult subjects currently or recently infected with P vivax and by 3:1 in healthy residents in the same endemic communities. We concluded that malaria can drive classical MBCs to differentiate into functionally impaired MBCs not only in subjects repeatedly exposed to P falciparum, but also in subjects living in areas with low levels of P vivax transmission in the Amazon, leading to an impaired B‐cell memory that may affect both naturally acquired and vaccine‐induced immunity.

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“…Down selection of P. vivax antigens could represent a challenge due to the technical difficulties and limitations presented by the lack of an in vitro culture system for this parasite species. Previously, naturally acquired antibodies to the P. vivax merozoite surface protein 1 (Pv-MSP1) [34] and binding-inhibitory antibodies response to P. vivax Duffy binding protein (PvDBP) [35] have been associated with reduced risk of P. vivax clinical manifestations in individuals from the Brazilian Amazon region. In addition, the contribution of antibody titers to the acquisition of protection against clinical disease has been assessed in a cohort of children from PNG.…”

Section: Discussionmentioning

confidence: 99%

Natural immune response to Plasmodium vivax alpha-helical coiled coil protein motifs and its association with the risk of P. vivax malaria

et al. 2017

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Protein α-helical coiled coil structures are known to induce antibodies able to block critical functions in different pathogens. In a previous study, a total of 50 proteins of Plasmodium vivax erythrocytic asexual stages containing α-helical coiled coil structural motifs were identified in silico, and the corresponding peptides were chemically synthesized. A total of 43 peptides were recognized by naturally acquired antibodies in plasma samples from both Papua New Guinea (PNG) and Colombian adult donors. In this study, the association between IgG antibodies to these peptides and clinical immunity was further explored by measuring total IgG antibody levels to 24 peptides in baseline samples from a longitudinal study of children aged 1–3 years (n = 164) followed for 16 months. Samples were reactive to all peptides tested. Eight peptides were recognized by >50% of individuals, whereas only one peptide had < 20% reactivity. Children infected at baseline were seropositive to 23/24 peptides. No significant association was observed between antibody titers and age or molecular force of infection, suggesting that antibody levels had already reached an equilibrium. There was a strong association between antibody levels to all peptides and protection against P. vivax clinical episodes during the 16 months follow-up. These results suggest that the selected coiled coil antigens might be good markers of both exposure and acquired immunity to P. vivax malaria, and further preclinical investigation should be performed to determine their potential as P. vivax vaccine antigens.

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Naturally Acquired Binding-Inhibitory Antibodies toPlasmodium vivaxDuffy Binding Protein and Clinical Immunity to Malaria in Rural Amazonians

Abstract: Strong naturally acquired BIAb responses are associated with a reduced risk of clinical P. vivax malaria in rural Amazonians.

Cited by 45 publications

References 28 publications

Amplification of Duffy binding protein-encoding gene allows Plasmodium vivax to evade host anti-DBP humoral immunity

Amplification of Duffy binding protein-encoding gene allows Plasmodium vivax to evade host anti-DBP humoral immunity

Apical membrane protein 1‐specific antibody profile and temporal changes in peripheral blood B‐cell populations in Plasmodium vivax malaria

Natural immune response to Plasmodium vivax alpha-helical coiled coil protein motifs and its association with the risk of P. vivax malaria

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