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Plasmodium vivax Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children.

Identifieur interne : 001914 ( PubMed/Curation ); précédent : 001913; suivant : 001915

Plasmodium vivax Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children.

Auteurs : Camila T. França [Australie] ; Wen-Qiang He [Australie] ; Jakub Gruszczyk [Australie] ; Nicholas T Y. Lim [Australie] ; Enmoore Lin [Papouasie-Nouvelle-Guinée] ; Benson Kiniboro [Papouasie-Nouvelle-Guinée] ; Peter M. Siba [Papouasie-Nouvelle-Guinée] ; Wai-Hong Tham [Australie] ; Ivo Mueller [Australie]

Source :

RBID : pubmed:27677183

Abstract

Major gaps in our understanding of Plasmodium vivax biology and the acquisition of immunity to this parasite hinder vaccine development. P. vivax merozoites exclusively invade reticulocytes, making parasite proteins that mediate reticulocyte binding and/or invasion potential key vaccine or drug targets. While protein interactions that mediate invasion are still poorly understood, the P. vivax Reticulocyte-Binding Protein family (PvRBP) is thought to be involved in P. vivax restricted host-cell selectivity.

DOI: 10.1371/journal.pntd.0005014
PubMed: 27677183

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pubmed:27677183

Le document en format XML

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<div type="abstract" xml:lang="en">Major gaps in our understanding of Plasmodium vivax biology and the acquisition of immunity to this parasite hinder vaccine development. P. vivax merozoites exclusively invade reticulocytes, making parasite proteins that mediate reticulocyte binding and/or invasion potential key vaccine or drug targets. While protein interactions that mediate invasion are still poorly understood, the P. vivax Reticulocyte-Binding Protein family (PvRBP) is thought to be involved in P. vivax restricted host-cell selectivity.</div>
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<Month>09</Month>
<Day>27</Day>
</DateCreated>
<DateRevised>
<Year>2017</Year>
<Month>02</Month>
<Day>24</Day>
</DateRevised>
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<ISSN IssnType="Electronic">1935-2735</ISSN>
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<Volume>10</Volume>
<Issue>9</Issue>
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<Year>2016</Year>
<Month>Sep</Month>
</PubDate>
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<Title>PLoS neglected tropical diseases</Title>
<ISOAbbreviation>PLoS Negl Trop Dis</ISOAbbreviation>
</Journal>
<ArticleTitle>Plasmodium vivax Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children.</ArticleTitle>
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<Abstract>
<AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Major gaps in our understanding of Plasmodium vivax biology and the acquisition of immunity to this parasite hinder vaccine development. P. vivax merozoites exclusively invade reticulocytes, making parasite proteins that mediate reticulocyte binding and/or invasion potential key vaccine or drug targets. While protein interactions that mediate invasion are still poorly understood, the P. vivax Reticulocyte-Binding Protein family (PvRBP) is thought to be involved in P. vivax restricted host-cell selectivity.</AbstractText>
<AbstractText Label="METHODOLOGY/PRINCIPAL FINDINGS" NlmCategory="RESULTS">We assessed the binding specificity of five members of the PvRBP family (PvRBP1a, PvRBP1b, PvRBP2a, PvRBP2b, PvRBP2-P2 and a non-binding fragment of PvRBP2c) to normocytes or reticulocytes. PvRBP2b was identified as the only reticulocyte-specific binder (P<0.001), whereas the others preferentially bound to normocytes (PvRBP1a/b P≤0.034), or showed comparable binding to both (PvRBP2a/2-P2, P = 0.38). Furthermore, we measured levels of total and IgG subclasses 1, 2, 3 and 4 to the six PvRBPs in a cohort of young Papua New Guinean children, and assessed their relationship with prospective risk of P. vivax malaria. Children had substantial, highly correlated (rho = 0.49-0.82, P<0.001) antibody levels to all six PvRBPs, with dominant IgG1 and IgG3 subclasses. Both total IgG (Incidence Rate Ratio [IRR] 0.63-0.73, P = 0.008-0.041) and IgG1 (IRR 0.56-0.69, P = 0.001-0.035) to PvRBP2b and PvRBP1a were strongly associated with reduced risk of vivax-malaria, independently of age and exposure.</AbstractText>
<AbstractText Label="CONCLUSION/SIGNIFICANCE" NlmCategory="CONCLUSIONS">These results demonstrate a diversity of erythrocyte-binding phenotypes of PvRBPs, indicating binding to both reticulocyte-specific and normocyte-specific ligands. Our findings provide further insights into the naturally acquired immunity to P. vivax and highlight the importance of PvRBP proteins as targets of naturally acquired humoral immunity. In-depth studies of the role of PvRBPs in P. vivax invasion and functional validation of the role of anti-PvRBP antibodies in clinical immunity against P. vivax are now required to confirm the potential of the reticulocyte-binding PvRBP2b and PvRBP1a as vaccine candidate antigens.</AbstractText>
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<ForeName>Camila T</ForeName>
<Initials>CT</Initials>
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<Affiliation>Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Department of Medical Biology, University of Melbourne, Melbourne, Australia.</Affiliation>
</AffiliationInfo>
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<LastName>He</LastName>
<ForeName>Wen-Qiang</ForeName>
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<Affiliation>Department of Medical Biology, University of Melbourne, Melbourne, Australia.</Affiliation>
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<AffiliationInfo>
<Affiliation>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.</Affiliation>
</AffiliationInfo>
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</AffiliationInfo>
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<ForeName>Peter M</ForeName>
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<LastName>Tham</LastName>
<ForeName>Wai-Hong</ForeName>
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<AffiliationInfo>
<Affiliation>Department of Medical Biology, University of Melbourne, Melbourne, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.</Affiliation>
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<Affiliation>Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Department of Medical Biology, University of Melbourne, Melbourne, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Malaria Parasites and Hosts Unit, Department of Parasites and Insect Vectors, Pasteur Institute, Paris, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Barcelona Institute of Global Health (ISGLOBAL), Barcelona, Spain.</Affiliation>
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<CoiStatement>The authors have declared that no competing interests exist.</CoiStatement>
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