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Udgivet

Antibodies to Intercellular Adhesion Molecule 1-Binding Plasmodium falciparum Erythrocyte Membrane Protein 1-DBLβ Are Biomarkers of Protective Immunity to Malaria in a Cohort of Young Children from Papua New Guinea

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. A vaccine targeted specifically to prevent cerebral malaria - is there hope?

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Parasites Causing Cerebral Falciparum Malaria Bind Multiple Endothelial Receptors and Express EPCR and ICAM-1-Binding PfEMP1

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Sofonias K Tessema
  • Digjaya Utama
  • Olga Chesnokov
  • Anthony N Hodder
  • Clara S Lin
  • G L Abby Harrison
  • Jakob S Jespersen
  • Bent Petersen
  • Livingstone Tavul
  • Peter Siba
  • Dominic Kwiatkowski
  • Thomas Lavstsen
  • Diana S Hansen
  • Andrew V Oleinikov
  • Ivo Mueller
  • Alyssa E Barry
Vis graf over relationer

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates parasite sequestration to the cerebral microvasculature via binding of DBLβ domains to intercellular adhesion molecule 1 (ICAM1) and is associated with severe cerebral malaria. In a cohort of 187 young children from Papua New Guinea (PNG), we examined baseline levels of antibody to the ICAM1-binding PfEMP1 domain, DBLβ3PF11_0521, in comparison to four control antigens, including NTS-DBLα and CIDR1 domains from another group A variant and a group B/C variant. Antibody levels for the group A antigens were strongly associated with age and exposure. Antibody responses to DBLβ3PF11_0521 were associated with a 37% reduced risk of high-density clinical malaria in the follow-up period (adjusted incidence risk ratio [aIRR] = 0.63 [95% confidence interval {CI}, 0.45 to 0.88; P = 0.007]) and a 25% reduction in risk of low-density clinical malaria (aIRR = 0.75 [95% CI, 0.55 to 1.01; P = 0.06]), while there was no such association for other variants. Children who experienced severe malaria also had significantly lower levels of antibody to DBLβ3PF11_0521 and the other group A domains than those that experienced nonsevere malaria. Furthermore, a subset of PNG DBLβ sequences had ICAM1-binding motifs, formed a distinct phylogenetic cluster, and were similar to sequences from other areas of endemicity. PfEMP1 variants associated with these DBLβ domains were enriched for DC4 and DC13 head structures implicated in endothelial protein C receptor (EPCR) binding and severe malaria, suggesting conservation of dual binding specificities. These results provide further support for the development of specific classes of PfEMP1 as vaccine candidates and as biomarkers for protective immunity against clinical P. falciparum malaria.

OriginalsprogEngelsk
TidsskriftInfection and Immunity
Vol/bind86
Udgave nummer8
Sider (fra-til)e00485-17
ISSN0019-9567
DOI
StatusUdgivet - aug. 2018

ID: 56466707