Protective immunity against severe malaria in children is associated with a limited repertoire of antibodies to conserved PfEMP1 variants

Tessema, Sofonias K., Nakajima, Rie, Jasinskas, Algis, Monk, Stephanie L., Lekieffre, Lea, Lin, Enmoore, Kiniboro, Benson, Proietti, Carla, Siba, Peter, Felgner, Philip L., Doolan, Denise L., Mueller, Ivo, and Barry, Alyssa E. (2019) Protective immunity against severe malaria in children is associated with a limited repertoire of antibodies to conserved PfEMP1 variants. Cell Host & Microbe, 26 (5). 13. 579-590.e5.

[img] PDF (Published Version)
Restricted to Repository staff only

View at Publisher Website: https://doi.org/10.1016/j.chom.2019.10.0...
 
5
1


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 DBL alpha 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 DBL alpha 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.

Item ID: 61126
Item Type: Article (Research - C1)
ISSN: 1934-6069
Keywords: malaria, severe malaria, Plasmodium, falciparum, PfEMP1, var genes, diversity, antibodies, immunity, vaccine, biomarker
Copyright Information: © 2019 Elsevier Inc
Date Deposited: 04 Dec 2019 07:44
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110705 Humoural Immunology and Immunochemistry @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
Downloads: Total: 1
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page