Publications & Reports

Protective Immunity against Severe Malaria in Children Is Associated with a Limited Repertoire of Antibodies to Conserved PfEMP1 Variants.

Sofonias K Tessema, Rie Nakajima, Algis Jasinskas, Stephanie L Monk, Lea Lekieffre, Enmoore Lin, Benson Kiniboro, Carla Proietti, Peter Siba, Philip L Felgner, Denise L Doolan, Ivo Mueller, Alyssa E Barry
Division of Population Health and Immunity, The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, VIC, Australia; Department of Medical Biology, University of Melbourne, Melbourne 3000, VIC, Australia.

Abstract

Extreme diversity of the major Plasmodium falciparum antigen, PfEMP1, poses a barrier to identifying targets of immunity to malaria. Here, we used protein microarrays containing hundreds of variants of the DBLalpha domain of PfEMP1 to cover the diversity of Papua New Guinean (PNG) parasites. Probing the plasma of a longitudinal cohort of malaria-exposed PNG children showed that group 2 DBLalpha antibodies were moderately associated with a lower risk of uncomplicated malaria, whereas individual variants were only weakly associated with clinical immunity. In contrast, antibodies to 85 individual group 1 and 2 DBLalpha variants were associated with a 70%-100% reduction in severe malaria. Of these, 17 variants were strong predictors of severe malaria. Analysis of full-length PfEMP1 sequences from PNG samples shows that these 17 variants are linked to pathogenic CIDR domains. This suggests that whereas immunity to uncomplicated malaria requires a broad repertoire of antibodies, immunity to severe malaria targets a subset of conserved variants. These findings provide insights into antimalarial immunity and potential antibody biomarkers for disease risk.

Publication

  • Journal: Cell Host & Microbe
  • Published: 13/11/2019
  • Volume: 26
  • Issue: 5
  • Pagination: 579-590.e5

Author