Evidence map›Paper›PMID 36333336›Full record

ArticleNPJ vaccines2022

Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver.

Blandine Franke-Fayard, Catherin Marin-Mogollon, Fiona J A Geurten, Séverine Chevalley-Maurel, Jai Ramesar, Hans Kroeze, Els Baalbergen, Els Wessels, Ludivine Baron, Valérie Soulard and 21 more

Open access · goldAbstract read
In one paragraph

Article in NPJ vaccines, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
6.6field-weighted citation impact, top 3% 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

23 citing papers in PubMed, 35 citations in OpenAlex.

  1. Trial
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  9. Parasitology · 2025
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  11. Early Activation of Lung CD8Pathogens & immunity · 2025
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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

31 authors at 12 institutions in 8 countries.

Blandine Franke-FayardMalaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands. bfranke@lumc.nl.ORCID http://orcid.org/0000-0001-6041-4182
Catherin Marin-MogollonMalaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands.
Fiona J A GeurtenMalaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands.
Séverine Chevalley-MaurelMalaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands.
Jai RamesarMalaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands.
Hans KroezeMalaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands.
Els BaalbergenMalaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands.
Els WesselsDepartment of Medical Microbiology, Leiden University Medical Center, 2300 RC, Leiden, the Netherlands.
Ludivine BaronSorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National pour la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, CIMI, Paris, France.
Valérie SoulardSorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National pour la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, CIMI, Paris, France.
Thomas MartinsonVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA.
Maya AleshnickVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA.ORCID http://orcid.org/0000-0001-5471-4242
Antonius T G HuijsTropIQ Health Sciences, Nijmegen, the Netherlands.
Amit K SubudhiPathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
Yukiko MiyazakiMalaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands.
Ahmad Syibli OthmanUniversiti Sultan Zainal Abidin, Faculty of Health Sciences, Terengganu, Malaysia.ORCID http://orcid.org/0000-0002-2020-900X
Surendra Kumar KolliMalaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0001-6125-0036
Olivia A C LamersMalaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands.
Magali RoquesInstitute of Cell Biology, University of Bern, Bern, Switzerland.
Rebecca R StanwayInstitute of Cell Biology, University of Bern, Bern, Switzerland.
Sean C MurphyDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-2048-0131
Lander FoquetYecuris Corporation, Tualatin, OR, USA.
Diana MoitaInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
António M MendesInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.ORCID http://orcid.org/0000-0001-6562-5325
Miguel PrudêncioInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.ORCID http://orcid.org/0000-0003-1746-6029
Koen J DecheringTropIQ Health Sciences, Nijmegen, the Netherlands.ORCID http://orcid.org/0000-0002-8124-4634
Volker T HeusslerInstitute of Cell Biology, University of Bern, Bern, Switzerland.
Arnab PainPathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
Brandon K WilderVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA.
Meta RoestenbergMalaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands. M.Roestenberg@lumc.nl.ORCID http://orcid.org/0000-0002-5052-2830
Chris J JanseMalaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands. c.j.janse@lumc.nl.ORCID http://orcid.org/0000-0002-6410-6205
Leiden University Medical Center · NLOregon Health & Science University · USUniversity of Bern · CHUniversity of Lisbon · PTCentre National de la Recherche Scientifique · FRTropIQ Health Sciences · NLHokkaido University · JPKing Abdullah University of Science and Technology · SASultan Zainal Abidin University · MYUniversity of South Florida · USUniversity of Washington · USYecuris (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Whole-sporozoite (WSp) malaria vaccines induce protective immune responses in animal malaria models and in humans. A recent clinical trial with a WSp vaccine comprising genetically attenuated parasites (GAP) which arrest growth early in the liver (PfSPZ-GA1), showed that GAPs can be safely administered to humans and immunogenicity is comparable to radiation-attenuated PfSPZ Vaccine. GAPs that arrest late in the liver stage (LA-GAP) have potential for increased potency as shown in rodent malaria models. Here we describe the generation of four putative P. falciparum LA-GAPs, generated by CRISPR/Cas9-mediated gene deletion. One out of four gene-deletion mutants produced sporozoites in sufficient numbers for further preclinical evaluation. This mutant, PfΔmei2, lacking the mei2-like RNA gene, showed late liver growth arrest in human liver-chimeric mice with human erythrocytes, absence of unwanted genetic alterations and sensitivity to antimalarial drugs. These features of PfΔmei2 make it a promising vaccine candidate, supporting further clinical evaluation. PfΔmei2 (GA2) has passed regulatory approval for safety and efficacy testing in humans based on the findings reported in this study.

Identifiers

PMID36333336
PMCPMC9636417
OpenAlexW4308210851

What OpenQuestion holds

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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.