Evidence map›Paper›PMID 25786180›Full record

Trial reportImmunity2015

Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria.

Michelle J Boyle, Linda Reiling, Gaoqian Feng, Christine Langer, Faith H Osier, Harvey Aspeling-Jones, Yik Sheng Cheng, Janine Stubbs, Kevin K A Tetteh, David J Conway and 5 more

Abstract readClinical Trial
In one paragraph

Trial report in Immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
190citing papers in PubMed, 1 pooled it
–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

190 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  17. Naturally acquired antibodies toFrontiers in immunology · 2026
    Article
  18. The N-terminal region of malaria vaccine candidatebioRxiv : the preprint server for biology · 2025
    Article
  19. Article
  20. Article

130 more citing papers are in PubMed but not listed here.

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

15 authors.

Michelle J BoyleThe Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, VIC 3004, Australia; Department of Medical Biology, University of Melbourne, Royal Parade, Melbourne, VIC 3010, Australia.
Linda ReilingThe Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, VIC 3004, Australia.
Gaoqian FengThe Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, VIC 3004, Australia.
Christine LangerThe Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, VIC 3004, Australia.
Faith H OsierCentre for Geographic Medicine Research, Kenya Medical Research Institute, Coast, PO Box 230, 80108 Kilifi, Kenya.
Harvey Aspeling-JonesLondon School of Hygiene and Tropical Medicine, Keppel Street, London WC1E7HT, UK.
Yik Sheng ChengThe Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, VIC 3004, Australia; Department of Medical Biology, University of Melbourne, Royal Parade, Melbourne, VIC 3010, Australia.
Janine StubbsThe Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, VIC 3004, Australia.
Kevin K A TettehLondon School of Hygiene and Tropical Medicine, Keppel Street, London WC1E7HT, UK.
David J ConwayLondon School of Hygiene and Tropical Medicine, Keppel Street, London WC1E7HT, UK.
James S McCarthyQIMR Berghofer Medical Research Institute, University of Queensland, 300 Herston Road, Herston, QLD 4006, Australia.
Ivo MullerWalter and Eliza Hall Institute, Royal Parade, Melbourne, VIC 3050, Australia.
Kevin MarshCentre for Geographic Medicine Research, Kenya Medical Research Institute, Coast, PO Box 230, 80108 Kilifi, Kenya.
Robin F AndersDepartment of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
James G BeesonThe Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, VIC 3004, Australia; Department of Microbiology, Monash University, Clayton, VIC 3800, Australia. Electronic address: beeson@burnet.edu.au.

Funding

Wellcome Trust 092654
6 · The paper itself

Abstract

Antibodies play major roles in immunity to malaria; however, a limited understanding of mechanisms mediating protection is a major barrier to vaccine development. We have demonstrated that acquired human anti-malarial antibodies promote complement deposition on the merozoite to mediate inhibition of erythrocyte invasion through C1q fixation and activation of the classical complement pathway. Antibody-mediated complement-dependent (Ab-C') inhibition was the predominant invasion-inhibitory activity of human antibodies; most antibodies were non-inhibitory without complement. Inhibitory activity was mediated predominately via C1q fixation, and merozoite surface proteins 1 and 2 were identified as major targets. Complement fixation by antibodies was very strongly associated with protection from both clinical malaria and high-density parasitemia in a prospective longitudinal study of children. Ab-C' inhibitory activity could be induced by human immunization with a candidate merozoite surface-protein vaccine. Our findings demonstrate that human anti-malarial antibodies have evolved to function by fixing complement for potent invasion-inhibitory activity and protective immunity.

Indexed as

AdolescentAnimalsAntibodies, ProtozoanAntigens, ProtozoanChildChild, PreschoolComplement C1qComplement Fixation TestsComplement Pathway, ClassicalErythrocytesFemaleGene ExpressionHost-Pathogen InteractionsHumansImmunoglobulin GMalaria, FalciparumAntibodies, ProtozoanAntigens, ProtozoanComplement C1qImmunoglobulin GMalaria VaccinesMerozoite Surface Protein 1merozoite surface protein 2, PlasmodiumProtozoan Proteins

Identifiers

PMID25786180
PMCPMC4372259

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.