Plasmodium vivax Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children
Identifieur interne : 002506 ( Main/Exploration ); précédent : 002505; suivant : 002507Plasmodium 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, France, Espagne]Source :
- PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2016.
Abstract
Major gaps in our understanding of
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
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
Url:
DOI: 10.1371/journal.pntd.0005014
PubMed: 27677183
PubMed Central: 5038947
Affiliations:
- Australie, Espagne, France, Papouasie-Nouvelle-Guinée
- Catalogne, Victoria (État), Île-de-France
- Barcelone, Melbourne, Paris
- Université de Melbourne
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Le document en format XML
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Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children</title>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>Plasmodium vivax</italic>
Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children</title>
<author><name sortKey="Franca, Camila T" sort="Franca, Camila T" uniqKey="Franca C" first="Camila T." last="França">Camila T. França</name>
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<author><name sortKey="Lim, Nicholas T Y" sort="Lim, Nicholas T Y" uniqKey="Lim N" first="Nicholas T. Y." last="Lim">Nicholas T. Y. Lim</name>
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<author><name sortKey="Lin, Enmoore" sort="Lin, Enmoore" uniqKey="Lin E" first="Enmoore" last="Lin">Enmoore Lin</name>
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<author><name sortKey="Kiniboro, Benson" sort="Kiniboro, Benson" uniqKey="Kiniboro B" first="Benson" last="Kiniboro">Benson Kiniboro</name>
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<author><name sortKey="Siba, Peter M" sort="Siba, Peter M" uniqKey="Siba P" first="Peter M." last="Siba">Peter M. Siba</name>
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</nlm:aff>
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<author><name sortKey="Tham, Wai Hong" sort="Tham, Wai Hong" uniqKey="Tham W" first="Wai-Hong" last="Tham">Wai-Hong Tham</name>
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<author><name sortKey="Mueller, Ivo" sort="Mueller, Ivo" uniqKey="Mueller I" first="Ivo" last="Mueller">Ivo Mueller</name>
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</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Malaria Parasites and Hosts Unit, Department of Parasites and Insect Vectors, Pasteur Institute, Paris</wicri:regionArea>
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<settlement type="city">Paris</settlement>
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</nlm:aff>
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<series><title level="j">PLoS Neglected Tropical Diseases</title>
<idno type="ISSN">1935-2727</idno>
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<front><div type="abstract" xml:lang="en"><sec id="sec001"><title>Background</title>
<p>Major gaps in our understanding of <italic>Plasmodium vivax</italic>
biology and the acquisition of immunity to this parasite hinder vaccine development. <italic>P</italic>
. <italic>vivax</italic>
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 <italic>P</italic>
. <italic>vivax</italic>
Reticulocyte-Binding Protein family (PvRBP) is thought to be involved in <italic>P</italic>
. <italic>vivax</italic>
restricted host-cell selectivity.</p>
</sec>
<sec id="sec002"><title>Methodology/Principal findings</title>
<p>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 <italic>P</italic>
. <italic>vivax</italic>
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.</p>
</sec>
<sec id="sec003"><title>Conclusion/Significance</title>
<p>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 <italic>P</italic>
. <italic>vivax</italic>
and highlight the importance of PvRBP proteins as targets of naturally acquired humoral immunity. In-depth studies of the role of PvRBPs in <italic>P</italic>
. <italic>vivax</italic>
invasion and functional validation of the role of anti-PvRBP antibodies in clinical immunity against <italic>P</italic>
. <italic>vivax</italic>
are now required to confirm the potential of the reticulocyte-binding PvRBP2b and PvRBP1a as vaccine candidate antigens.</p>
</sec>
</div>
</front>
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</author>
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</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tham, Wh" uniqKey="Tham W">WH Tham</name>
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</analytic>
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<author><name sortKey="Barlow, Pn" uniqKey="Barlow P">PN Barlow</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Crosnier, C" uniqKey="Crosnier C">C Crosnier</name>
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</biblStruct>
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<author><name sortKey="Goodman, Al" uniqKey="Goodman A">AL Goodman</name>
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</div1>
</back>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>Espagne</li>
<li>France</li>
<li>Papouasie-Nouvelle-Guinée</li>
</country>
<region><li>Catalogne</li>
<li>Victoria (État)</li>
<li>Île-de-France</li>
</region>
<settlement><li>Barcelone</li>
<li>Melbourne</li>
<li>Paris</li>
</settlement>
<orgName><li>Université de Melbourne</li>
</orgName>
</list>
<tree><country name="Australie"><region name="Victoria (État)"><name sortKey="Franca, Camila T" sort="Franca, Camila T" uniqKey="Franca C" first="Camila T." last="França">Camila T. França</name>
</region>
<name sortKey="Franca, Camila T" sort="Franca, Camila T" uniqKey="Franca C" first="Camila T." last="França">Camila T. França</name>
<name sortKey="Gruszczyk, Jakub" sort="Gruszczyk, Jakub" uniqKey="Gruszczyk J" first="Jakub" last="Gruszczyk">Jakub Gruszczyk</name>
<name sortKey="He, Wen Qiang" sort="He, Wen Qiang" uniqKey="He W" first="Wen-Qiang" last="He">Wen-Qiang He</name>
<name sortKey="He, Wen Qiang" sort="He, Wen Qiang" uniqKey="He W" first="Wen-Qiang" last="He">Wen-Qiang He</name>
<name sortKey="Lim, Nicholas T Y" sort="Lim, Nicholas T Y" uniqKey="Lim N" first="Nicholas T. Y." last="Lim">Nicholas T. Y. Lim</name>
<name sortKey="Mueller, Ivo" sort="Mueller, Ivo" uniqKey="Mueller I" first="Ivo" last="Mueller">Ivo Mueller</name>
<name sortKey="Mueller, Ivo" sort="Mueller, Ivo" uniqKey="Mueller I" first="Ivo" last="Mueller">Ivo Mueller</name>
<name sortKey="Tham, Wai Hong" sort="Tham, Wai Hong" uniqKey="Tham W" first="Wai-Hong" last="Tham">Wai-Hong Tham</name>
<name sortKey="Tham, Wai Hong" sort="Tham, Wai Hong" uniqKey="Tham W" first="Wai-Hong" last="Tham">Wai-Hong Tham</name>
</country>
<country name="Papouasie-Nouvelle-Guinée"><noRegion><name sortKey="Lin, Enmoore" sort="Lin, Enmoore" uniqKey="Lin E" first="Enmoore" last="Lin">Enmoore Lin</name>
</noRegion>
<name sortKey="Kiniboro, Benson" sort="Kiniboro, Benson" uniqKey="Kiniboro B" first="Benson" last="Kiniboro">Benson Kiniboro</name>
<name sortKey="Siba, Peter M" sort="Siba, Peter M" uniqKey="Siba P" first="Peter M." last="Siba">Peter M. Siba</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Mueller, Ivo" sort="Mueller, Ivo" uniqKey="Mueller I" first="Ivo" last="Mueller">Ivo Mueller</name>
</region>
</country>
<country name="Espagne"><region name="Catalogne"><name sortKey="Mueller, Ivo" sort="Mueller, Ivo" uniqKey="Mueller I" first="Ivo" last="Mueller">Ivo Mueller</name>
</region>
</country>
</tree>
</affiliations>
</record>
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