Evidence map›Paper›PMID 39174515›Full record

ArticleNature communications2024

A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites.

Dimuthu Angage, Jill Chmielewski, Janesha C Maddumage, Eva Hesping, Sabrina Caiazzo, Keng Heng Lai, Lee Ming Yeoh, Joseph Menassa, D Herbert Opi, Callum Cairns and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

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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

17 authors.

Dimuthu AngageDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Victoria, 3086, Australia.ORCID 0009-0009-4776-487X
Jill ChmielewskiResearch Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, 5005, Australia.
Janesha C MaddumageDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Victoria, 3086, Australia.
Eva HespingInfectious Diseases & Immune Defense Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052, Australia.
Sabrina CaiazzoInfectious Diseases & Immune Defense Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052, Australia.
Keng Heng LaiResearch Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, 5005, Australia.ORCID 0000-0002-2111-0466
Lee Ming YeohBurnet Institute, Melbourne, Victoria, 3004, Australia.ORCID 0000-0001-7872-762X
Joseph MenassaDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Victoria, 3086, Australia.
D Herbert OpiBurnet Institute, Melbourne, Victoria, 3004, Australia.ORCID 0000-0002-4589-4365
Callum CairnsDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Victoria, 3086, Australia.
Hamsa PuthalakathDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Victoria, 3086, Australia.ORCID 0000-0001-5178-1175
James G BeesonBurnet Institute, Melbourne, Victoria, 3004, Australia.ORCID 0000-0002-1018-7898
Marc KvansakulDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Victoria, 3086, Australia.ORCID 0000-0003-2639-2498
Justin A BoddeyInfectious Diseases & Immune Defense Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052, Australia.ORCID 0000-0001-7322-2040
Danny W WilsonResearch Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, 5005, Australia.ORCID 0000-0002-5073-1405
Robin F AndersDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Victoria, 3086, Australia.
Michael FoleyDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Victoria, 3086, Australia. m.foley@latrobe.edu.au.ORCID 0000-0003-1349-4698

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Apical membrane antigen-1 (AMA1) is a conserved malarial vaccine candidate essential for the formation of tight junctions with the rhoptry neck protein (RON) complex, enabling Plasmodium parasites to invade human erythrocytes, hepatocytes, and mosquito salivary glands. Despite its critical role, extensive surface polymorphisms in AMA1 have led to strain-specific protection, limiting the success of AMA1-based interventions beyond initial clinical trials. Here, we identify an i-body, a humanised single-domain antibody-like molecule that recognises a conserved pan-species conformational epitope in AMA1 with low nanomolar affinity and inhibits the binding of the RON2 ligand to AMA1. Structural characterisation indicates that the WD34 i-body epitope spans the centre of the conserved hydrophobic cleft in AMA1, where interacting residues are highly conserved among all Plasmodium species. Furthermore, we show that WD34 inhibits merozoite invasion of erythrocytes by multiple Plasmodium species and hepatocyte invasion by P. falciparum sporozoites. Despite a short half-life in mouse serum, we demonstrate that WD34 transiently suppressed P. berghei infections in female BALB/c mice. Our work describes the first pan-species AMA1 biologic with inhibitory activity against multiple life-cycle stages of Plasmodium. With improved pharmacokinetic characteristics, WD34 could be a potential immunotherapy against multiple species of Plasmodium.

Indexed as

Antigens, ProtozoanErythrocytesLiverMembrane ProteinsMice, Inbred BALB CProtozoan ProteinsAnimalsCross ReactionsEpitopesFemaleHepatocytesHumansMalariaMalaria VaccinesMerozoitesMiceAntigens, Protozoanapical membrane antigen I, PlasmodiumEpitopesMalaria VaccinesMembrane ProteinsProtozoan Proteins

Identifiers

PMID39174515
PMCPMC11341838

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.