A systems serology approach to identifying key antibody correlates of protection from cerebral malaria in Malawian children

IS Walker; S Dini; EH Aitken; T Damelang; W Hasang; A Alemu; ATR Jensen; JS Rambhatla; DH Opi; MF Duffy; E Takashima; V Harawa; T Tsuboi; JA Simpson; W Mandala; TE Taylor; KB Seydel; AW Chung; SJ Rogerson

Journal article

A systems serology approach to identifying key antibody correlates of protection from cerebral malaria in Malawian children

IS Walker, S Dini, EH Aitken, T Damelang, W Hasang, A Alemu, ATR Jensen, JS Rambhatla, DH Opi, MF Duffy, E Takashima, V Harawa, T Tsuboi, JA Simpson, W Mandala, TE Taylor, KB Seydel, AW Chung, SJ Rogerson

BMC Medicine | BMC | Published : 2024

DOI: 10.1186/s12916-024-03604-8

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Abstract

Background: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins are expressed on the surface of infected erythrocytes, mediating parasite sequestration in the vasculature. PfEMP1 is a major target of protective antibodies, but the features of the antibody response are poorly defined. Methods: In Malawian children with cerebral or uncomplicated malaria, we characterized the antibody response to 39 recombinant PfEMP1 Duffy binding like (DBL) domains or cysteine-rich interdomain regions (CIDRs) in detail, including measures of antibody classes, subclasses, and engagement with Fcγ receptors and complement. Using elastic net regularized logistic regression, we identified a comb..

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University of Melbourne Researchers

Isobel Walker Author

Saber Dini Author

Elizabeth Aitken Author

Wina Hasang Author

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Grants

Awarded by University of Melbourne

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (NHMRC) through grants GNT1061993 and GNT1092789 to SJR. ATRJ was supported by the Lundbeck Foundation (R313-2019-322). JAS and AWC are supported by NHMRC Investigator Awards 1196068 (JAS) and 2008092 (AWC). ISW was supported by a University of Melbourne Research Training Program Scholarship and Rowden White Scholarship.