Evidence map›Paper›PMID 30333026›Full record

ArticleMalaria journal2018

A recombinant antibody against Plasmodium vivax UIS4 for distinguishing replicating from dormant liver stages.

Carola Schafer, Nicholas Dambrauskas, Ryan W Steel, Sara Carbonetti, Vorada Chuenchob, Erika L Flannery, Vladimir Vigdorovich, Brian G Oliver, Wanlapa Roobsoong, Steven P Maher and 5 more

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
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

26 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
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  3. MaRNAV-1, an intracellular virus ofbioRxiv : the preprint server for biology · 2026
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  5. Simian iPS-derived hepatocytes supportFrontiers in cellular and infection microbiology · 2026
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  7. TwoResearch square · 2025
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  9. A Drug Repurposing Approach Reveals Targetable Epigenetic Pathways inbioRxiv : the preprint server for biology · 2024
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  12. Review
  13. Cryopreservation ofPathogens (Basel, Switzerland) · 2022
    Article
  14. Molecular therapy. Methods & clinical development · 2022
    Article
  15. Review
  16. iScience · 2022
    Article
  17. Article
  18. Liver-stage fate determination inFrontiers in microbiology · 2022
    Article
  19. Single-cell RNA profiling ofFrontiers in cellular and infection microbiology · 2022
    Article
  20. Article
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 at 4 institutions in 3 countries.

Carola SchaferCenter for Infectious Disease Research, Seattle, WA, USA.
Nicholas DambrauskasCenter for Infectious Disease Research, Seattle, WA, USA.
Ryan W SteelCenter for Infectious Disease Research, Seattle, WA, USA.
Sara CarbonettiCenter for Infectious Disease Research, Seattle, WA, USA.
Vorada ChuenchobCenter for Infectious Disease Research, Seattle, WA, USA.
Erika L FlanneryCenter for Infectious Disease Research, Seattle, WA, USA.
Vladimir VigdorovichCenter for Infectious Disease Research, Seattle, WA, USA.
Brian G OliverCenter for Infectious Disease Research, Seattle, WA, USA.
Wanlapa RoobsoongMahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Steven P MaherCenter for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA.
Dennis KyleCenter for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA.
Jetsumon SattabongkotMahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Stefan H I KappeCenter for Infectious Disease Research, Seattle, WA, USA.
Sebastian A MikolajczakCenter for Infectious Disease Research, Seattle, WA, USA. Sebastian.mikolajczak@cidresearch.org.
D Noah SatherCenter for Infectious Disease Research, Seattle, WA, USA. noah.sather@seattlechildrens.org.ORCID http://orcid.org/0000-0002-9128-172X
Center for Infectious Disease Research · USMahidol University · THUniversity of Georgia · USInfectious Disease Research Institute · US

Funding

Infection-blocking antibody targets for malariaR01AI117234 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI KAPPE, STEFAN HI, SATHER, D. NOAH · 2016 to 2020
$4.2M
Deutsche Forschungsgemeinschaft SCHA 2047/1-1National Institute of Allergy and Infectious Diseases AI117234NIAID NIH HHS R01 AI117234
6 · The paper itself

Abstract

backgroundPlasmodium vivax is the most geographically widespread of the human malaria parasites, causing 50,000 to 100,000 deaths annually. Plasmodium vivax parasites have the unique feature of forming dormant liver stages (hypnozoites) that can reactivate weeks or months after a parasite-infected mosquito bite, leading to new symptomatic blood stage infections. Efforts to eliminate P. vivax malaria likely will need to target the persistent hypnozoites in the liver. Therefore, research on P. vivax liver stages necessitates a marker for clearly distinguishing between actively replicating parasites and dormant hypnozoites. Hypnozoites possess a densely fluorescent prominence in the parasitophorous vacuole membrane (PVM) when stained with antibodies against the PVM-resident protein Upregulated in Infectious Sporozoites 4 (PvUIS4), resulting in a key feature recognizable for quantification of hypnozoites. Thus, PvUIS4 staining, in combination with the characteristic small size of the parasite, is currently the only hypnozoite-specific morphological marker available.

resultsHere, the generation and validation of a recombinant monoclonal antibody against PvUIS4 (α-rUIS4 mAb) is described. The variable heavy and light chain domains of an α-PvUIS4 hybridoma were cloned into murine IgG1 and IgK expression vectors. These expression plasmids were co-transfected into HEK293 cells and mature IgG was purified from culture supernatants. It is shown that the α-rUIS4 mAb binds to its target with high affinity. It reliably stains the schizont PVM and the hypnozoite-specific PVM prominence, enabling the visual differentiation of hypnozoites from replicating liver stages by immunofluorescence assays in different in vitro settings, as well as in liver sections from P. vivax infected liver-chimeric mice. The antibody functions reliably against all four parasite isolates tested and will be an important tool in the identification of the elusive hypnozoite.

conclusionsThe α-rUIS4 mAb is a versatile tool for distinguishing replicating P. vivax liver stages from dormant hypnozoites, making it a valuable resource that can be deployed throughout laboratories worldwide.

Indexed as

Antibodies, ProtozoanBiomarkersLiverPlasmodium vivaxSporozoitesAntibodies, ProtozoanBiomarkersHypnozoitePlasmodium vivaxRecombinant antibodyUIS4

Identifiers

PMID30333026
PMCPMC6192329
OpenAlexW2897508936

What OpenQuestion holds

Textmetadata
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.