Format

Send to

Choose Destination
Cell Host Microbe. 2019 Nov 13;26(5):579-590.e5. doi: 10.1016/j.chom.2019.10.012.

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

Author information

1
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.
2
Physiology & Biophysics Department, Vaccine R&D Center, University of California, Irvine, Irvine 92697, CA, USA.
3
Infectious Diseases Programme, QIMR Berghofer Medical Research Institute, Brisbane 4006, QLD, Australia.
4
Vector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Goroka 441, EHG, Papua New Guinea.
5
Infectious Diseases Programme, QIMR Berghofer Medical Research Institute, Brisbane 4006, QLD, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, QLD, Australia.
6
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; Department of Parasites and Insect Vectors, Institut Pasteur, Paris 75015, France.
7
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. Electronic address: a.barry@deakin.edu.au.

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 DBLα 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 DBLα 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 DBLα 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.

KEYWORDS:

PfEMP1; Plasmodium falciparum; antibodies; biomarker; diversity; immunity; malaria; severe malaria; vaccine; var genes

Comment in

PMID:
31726028
DOI:
10.1016/j.chom.2019.10.012

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center