Evidence map›Paper›PMID 34802442›Full record

Trial reportBMC medicine2021

Safety, infectivity and immunogenicity of a genetically attenuated blood-stage malaria vaccine.

Rebecca Webster, Silvana Sekuloski, Anand Odedra, Stephen Woolley, Helen Jennings, Fiona Amante, Katharine R Trenholme, Julie Healer, Alan F Cowman, Emily M Eriksson and 19 more

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in BMC medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

8 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Malaria Vaccines: Progress to Date.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023
    Review
  7. A genetically engineeredScience translational medicine · 2022
    Article
  8. 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

29 authors at 10 institutions in 2 countries.

Rebecca WebsterQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Silvana SekuloskiQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Anand OdedraQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Stephen WoolleyQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Helen JenningsQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Fiona AmanteQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Katharine R TrenholmeQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Julie HealerThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Alan F CowmanThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Emily M ErikssonThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Priyanka SatheCurrent address: Medicines Development for Global Health Limited, 18 Kavanagh Street, Southbank, Victoria, 3006, Australia.
Jocelyn PeningtonThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Adam J BlanchBio21 Molecular Science and Biotechnology Institute, Melbourne, Australia.
Matthew W A DixonBio21 Molecular Science and Biotechnology Institute, Melbourne, Australia.
Leann TilleyBio21 Molecular Science and Biotechnology Institute, Melbourne, Australia.
Michael F DuffyDepartment of Microbiology and Immunology, University of Melbourne, Melbourne, Australia.
Alister CraigLiverpool School of Tropical Medicine, Liverpool, UK.
Janet StormLiverpool School of Tropical Medicine, Liverpool, UK.
Jo-Anne ChanBurnet Institute, Melbourne, Australia.
Krystal EvansThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Anthony T PapenfussThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Louis SchofieldThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Paul GriffinQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Bridget E BarberQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Dean AndrewQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Michelle J BoyleQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Fabian de Labastida RiveraQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Christian EngwerdaQIMR Berghofer Medical Research Institute, Brisbane, Australia.
James S McCarthyQIMR Berghofer Medical Research Institute, Brisbane, Australia. james.mccarthy@unimelb.edu.au.
QIMR Berghofer Medical Research Institute · AUUniversity of Melbourne · AULiverpool School of Tropical Medicine · GBWalter and Eliza Hall Institute of Medical Research · AUAustralian Institute of Tropical Health and Medicine · AUBurnet Institute · AUGlaxoSmithKline (Australia) · AUMater Research · AUPeter Doherty Institute · AURoyal Navy · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThere is a clear need for novel approaches to malaria vaccine development. We aimed to develop a genetically attenuated blood-stage vaccine and test its safety, infectivity, and immunogenicity in healthy volunteers. Our approach was to target the gene encoding the knob-associated histidine-rich protein (KAHRP), which is responsible for the assembly of knob structures at the infected erythrocyte surface. Knobs are required for correct display of the polymorphic adhesion ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1), a key virulence determinant encoded by a repertoire of var genes.

methodsThe gene encoding KAHRP was deleted from P. falciparum 3D7 and a master cell bank was produced in accordance with Good Manufacturing Practice. Eight malaria naïve males were intravenously inoculated (day 0) with 1800 (2 subjects), 1.8 × 10

resultsNone of the subjects who were administered with 1800 or 1.8 × 10

conclusionsThis study represents the first clinical investigation of a genetically attenuated blood-stage human malaria vaccine. A P. falciparum 3D7 kahrp- strain was tested in vivo and found to be immunogenic but can lead to patent parasitemia at high doses.

trial registrationAustralian New Zealand Clinical Trials Registry (number: ACTRN12617000824369 ; date: 06 June 2017).

Indexed as

AntimalarialsMalariaMalaria, FalciparumMalaria VaccinesArtemetherArtemether, Lumefantrine Drug CombinationAustraliaHumansMalePlasmodium falciparumProtozoan ProteinsVaccine DevelopmentVaccines, AttenuatedAntimalarialsArtemetherArtemether, Lumefantrine Drug CombinationMalaria VaccinesProtozoan ProteinsVaccines, AttenuatedGenetically attenuatedKAHRPMalariaPfEMP1Plasmodium falciparumVaccine

Identifiers

PMID34802442
PMCPMC8606250
OpenAlexW3216416221

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.