Evidence map›Paper›PMID 39267089›Full record

ArticleBMC medicine2024

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

Isobel S Walker, Saber Dini, Elizabeth H Aitken, Timon Damelang, Wina Hasang, Agersew Alemu, Anja T R Jensen, Janavi S Rambhatla, D Herbert Opi, Michael F Duffy and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Malaria monoclonals block brain binding.Trends in parasitology · 2025
    Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Isobel S WalkerDepartment of Medicine, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.
Saber DiniCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, 3010, Australia.
Elizabeth H AitkenDepartment of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.
Timon DamelangDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.
Wina HasangDepartment of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.
Agersew AlemuDepartment of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.
Anja T R JensenCentre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Janavi S RambhatlaDepartment of Medicine, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.
D Herbert OpiDepartment of Medicine, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.
Michael F DuffyDepartment of Medicine, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.
Eizo TakashimaDivision of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan.
Visopo HarawaMalawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Takafumi TsuboiDivision of Cell-Free Sciences, Proteo-Science Center, Ehime University, Matsuyama, Japan.
Julie A SimpsonCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, 3010, Australia.
Wilson MandalaAcademy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi.
Terrie E TaylorBlantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi.
Karl B SeydelBlantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi.
Amy W ChungDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.
Stephen J RogersonDepartment of Medicine, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia. sroger@unimelb.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPlasmodium 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.

methodsIn 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 combination of seven antibody targets and Fc features that best distinguished between children with cerebral and uncomplicated malaria. To confirm the role of the selected targets and Fc features, we measured antibody-dependent neutrophil and THP-1 cell phagocytosis of intercellular adhesion molecule-1 (ICAM-1) and endothelial protein C (EPCR) co-binding infected erythrocytes.

resultsThe selected features distinguished between children with cerebral and uncomplicated malaria with 87% accuracy (median, 80-96% interquartile range) and included antibody to well-characterized DBLβ3 domains and a less well-characterized CIDRγ12 domain. The abilities of antibodies to engage C1q and FcγRIIIb, rather than levels of IgG, correlated with protection. In line with a role of FcγRIIIb binding antibodies to DBLβ3 domains, antibody-dependent neutrophil phagocytosis of ICAM-1 and EPCR co-binding IE was higher in uncomplicated malaria (15% median, 8-38% interquartile range) compared to cerebral malaria (7%, 30-15%, p < 0.001).

conclusionsAntibodies associated with protection from cerebral malaria target a subset of PfEMP1 domains. The Fc features of protective antibody response include engagement of FcγRIIIb and C1q, and ability to induce antibody-dependent neutrophil phagocytosis of infected erythrocytes. Identifying the targets and Fc features of protective immunity could facilitate the development of PfEMP1-based therapeutics for cerebral malaria.

Indexed as

Antibodies, ProtozoanMalaria, CerebralPlasmodium falciparumProtozoan ProteinsAntigens, ProtozoanChildChild, PreschoolEndothelial Protein C ReceptorErythrocytesFemaleHumansInfantIntercellular Adhesion Molecule-1Malaria, FalciparumMalawiMaleAntibodies, ProtozoanAntigens, ProtozoanEndothelial Protein C Receptorerythrocyte membrane protein 1, Plasmodium falciparumIntercellular Adhesion Molecule-1PROCR protein, humanProtozoan ProteinsAfricaAntibodyImmunityMalawiPlasmodium falciparum

Identifiers

PMID39267089
PMCPMC11396342

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.