Plasmodium vivax Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children
Identifieur interne : 002506 ( Main/Curation ); 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
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França</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff002"><addr-line>Department of Medical Biology, University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="He, Wen Qiang" sort="He, Wen Qiang" uniqKey="He W" first="Wen-Qiang" last="He">Wen-Qiang He</name><affiliation wicri:level="4"><nlm:aff id="aff002"><addr-line>Department of Medical Biology, University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Gruszczyk, Jakub" sort="Gruszczyk, Jakub" uniqKey="Gruszczyk J" first="Jakub" last="Gruszczyk">Jakub Gruszczyk</name><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Lim, Nicholas T Y" sort="Lim, Nicholas T Y" uniqKey="Lim N" first="Nicholas T. 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França</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff002"><addr-line>Department of Medical Biology, University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="He, Wen Qiang" sort="He, Wen Qiang" uniqKey="He W" first="Wen-Qiang" last="He">Wen-Qiang He</name><affiliation wicri:level="4"><nlm:aff id="aff002"><addr-line>Department of Medical Biology, University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Gruszczyk, Jakub" sort="Gruszczyk, Jakub" uniqKey="Gruszczyk J" first="Jakub" last="Gruszczyk">Jakub Gruszczyk</name><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><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><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Lin, Enmoore" sort="Lin, Enmoore" uniqKey="Lin E" first="Enmoore" last="Lin">Enmoore Lin</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Malaria Immuno-Epidemiology Unit, PNG Institute of Medical Research, Madang, Papua New Guinea</addr-line></nlm:aff><country xml:lang="fr">Papouasie-Nouvelle-Guinée</country><wicri:regionArea>Malaria Immuno-Epidemiology Unit, PNG Institute of Medical Research, Madang</wicri:regionArea><wicri:noRegion>Madang</wicri:noRegion></affiliation></author><author><name sortKey="Kiniboro, Benson" sort="Kiniboro, Benson" uniqKey="Kiniboro B" first="Benson" last="Kiniboro">Benson Kiniboro</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Malaria Immuno-Epidemiology Unit, PNG Institute of Medical Research, Madang, Papua New Guinea</addr-line></nlm:aff><country xml:lang="fr">Papouasie-Nouvelle-Guinée</country><wicri:regionArea>Malaria Immuno-Epidemiology Unit, PNG Institute of Medical Research, Madang</wicri:regionArea><wicri:noRegion>Madang</wicri:noRegion></affiliation></author><author><name sortKey="Siba, Peter M" sort="Siba, Peter M" uniqKey="Siba P" first="Peter M." last="Siba">Peter M. Siba</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Malaria Immuno-Epidemiology Unit, PNG Institute of Medical Research, Madang, Papua New Guinea</addr-line></nlm:aff><country xml:lang="fr">Papouasie-Nouvelle-Guinée</country><wicri:regionArea>Malaria Immuno-Epidemiology Unit, PNG Institute of Medical Research, Madang</wicri:regionArea><wicri:noRegion>Madang</wicri:noRegion></affiliation></author><author><name sortKey="Tham, Wai Hong" sort="Tham, Wai Hong" uniqKey="Tham W" first="Wai-Hong" last="Tham">Wai-Hong Tham</name><affiliation wicri:level="4"><nlm:aff id="aff002"><addr-line>Department of Medical Biology, University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Mueller, Ivo" sort="Mueller, Ivo" uniqKey="Mueller I" first="Ivo" last="Mueller">Ivo Mueller</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff002"><addr-line>Department of Medical Biology, University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>Malaria Parasites and Hosts Unit, Department of Parasites and Insect Vectors, Pasteur Institute, Paris, France</addr-line></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><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>Barcelona Institute of Global Health (ISGLOBAL), Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona Institute of Global Health (ISGLOBAL), Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author></analytic><series><title level="j">PLoS Neglected Tropical Diseases</title><idno type="ISSN">1935-2727</idno><idno type="eISSN">1935-2735</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><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><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Mueller, I" uniqKey="Mueller I">I Mueller</name></author><author><name sortKey="Galinski, Mr" uniqKey="Galinski M">MR Galinski</name></author><author><name sortKey="Baird, Jk" uniqKey="Baird J">JK Baird</name></author><author><name sortKey="Carlton, Jm" uniqKey="Carlton J">JM Carlton</name></author><author><name sortKey="Kochar, Dk" uniqKey="Kochar D">DK Kochar</name></author><author><name sortKey="Alonso, Pl" uniqKey="Alonso P">PL Alonso</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cowman, Af" 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Goodman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wright, Ke" uniqKey="Wright K">KE Wright</name></author><author><name sortKey="Hjerrild, Ka" uniqKey="Hjerrild K">KA Hjerrild</name></author><author><name sortKey="Bartlett, J" uniqKey="Bartlett J">J Bartlett</name></author><author><name sortKey="Douglas, Ad" uniqKey="Douglas A">AD Douglas</name></author><author><name sortKey="Jin, J" uniqKey="Jin J">J Jin</name></author><author><name sortKey="Brown, Re" uniqKey="Brown R">RE Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name></author><author><name sortKey="Xu, Y" uniqKey="Xu Y">Y Xu</name></author><author><name sortKey="Healer, J" uniqKey="Healer J">J Healer</name></author><author><name sortKey="Thompson, Jk" uniqKey="Thompson J">JK Thompson</name></author><author><name sortKey="Smith, Bj" uniqKey="Smith B">BJ Smith</name></author><author><name sortKey="Lawrence, Mc" uniqKey="Lawrence M">MC Lawrence</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Douglas, Ad" uniqKey="Douglas A">AD Douglas</name></author><author><name sortKey="Baldeviano, Gc" uniqKey="Baldeviano G">GC Baldeviano</name></author><author><name sortKey="Lucas, Cm" uniqKey="Lucas C">CM Lucas</name></author><author><name sortKey="Lugo Roman, La" uniqKey="Lugo Roman L">LA Lugo-Roman</name></author><author><name sortKey="Crosnier, C" uniqKey="Crosnier C">C Crosnier</name></author><author><name sortKey="Bartholdson, Sj" uniqKey="Bartholdson S">SJ Bartholdson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Douglas, Ad" uniqKey="Douglas A">AD Douglas</name></author><author><name sortKey="Williams, Ar" uniqKey="Williams A">AR Williams</name></author><author><name sortKey="Knuepfer, E" uniqKey="Knuepfer E">E Knuepfer</name></author><author><name sortKey="Illingworth, Jj" uniqKey="Illingworth J">JJ Illingworth</name></author><author><name sortKey="Furze, Jm" uniqKey="Furze J">JM Furze</name></author><author><name sortKey="Crosnier, C" uniqKey="Crosnier C">C Crosnier</name></author></analytic></biblStruct></listBibl></div1></back></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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