Evidence map›Paper›PMID 30081913›Full record

ArticleMalaria journal2018

A bioreactor system for the manufacture of a genetically modified Plasmodium falciparum blood stage malaria cell bank for use in a clinical trial.

Rebecca Pawliw, Rebecca Farrow, Silvana Sekuloski, Helen Jennings, Julie Healer, Thuan Phuong, Pri Sathe, Cielo Pasay, Krystal Evans, Alan F Cowman and 4 more

Abstract read
PubMed Full text at PMC Publisher
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 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Article
  4. Cultivation of Asexual Intraerythrocytic Stages ofPathogens (Basel, Switzerland) · 2023
    Review
  5. Article
  6. Safety Considerations for Malaria Volunteer Infection Studies: A Mini-Review.The American journal of tropical medicine and hygiene · 2020
    Review
  7. 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

14 authors.

Rebecca PawliwClinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, QLD, Australia.
Rebecca FarrowClinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, QLD, Australia.
Silvana SekuloskiClinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, QLD, Australia.
Helen JenningsClinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, QLD, Australia.
Julie HealerThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Thuan PhuongClinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, QLD, Australia.
Pri SatheThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Cielo PasayClinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, QLD, Australia.
Krystal EvansThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Alan F CowmanThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Louis SchofieldThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Nanhua ChenDepartment of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia.
James McCarthyClinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, QLD, Australia.
Katharine TrenholmeClinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, QLD, Australia. Katharine.Trenholme@qimrberghofer.edu.au.ORCID http://orcid.org/0000-0002-6397-8634

Funding

National Health and Medical Research Council 1041802National Health and Medical Research Council APP1002835National Health and Medical Research Council APP1055999
6 · The paper itself

Abstract

backgroundAlthough the use of induced blood stage malaria infection has proven to be a valuable tool for testing the efficacy of vaccines and drugs against Plasmodium falciparum, a limiting factor has been the availability of Good Manufacturing Practice (GMP)-compliant defined P. falciparum strains for in vivo use. The aim of this study was to develop a cost-effective method for the large-scale production of P. falciparum cell banks suitable for use in clinical trials.

methodsGenetically-attenuated parasites (GAP) were produced by targeted deletion of the gene encoding the knob associated histidine rich protein (kahrp) from P. falciparum strain 3D7. A GAP master cell bank (MCB) was manufactured by culturing parasites in an FDA approved single use, closed system sterile plastic bioreactor. All components used to manufacture the MCB were screened to comply with standards appropriate for in vivo use. The cryopreserved MCB was subjected to extensive testing to ensure GMP compliance for a phase 1 investigational product.

resultsTwo hundred vials of the GAP MCB were successfully manufactured. At harvest, the GAP MCB had a parasitaemia of 6.3%, with 96% of parasites at ring stage. Testing confirmed that all release criteria were met (sterility, absence of viral contaminants and endotoxins, parasite viability following cryopreservation, identity and anti-malarial drug sensitivity of parasites).

conclusionLarge-scale in vitro culture of P. falciparum parasites using a wave bioreactor can be achieved under GMP-compliant conditions. This provides a cost-effective methodology for the production of malaria parasites suitable for administration in clinical trials.

Indexed as

Microorganisms, Genetically-ModifiedPlasmodium falciparumAntimalarialsBiological Specimen BanksBioreactorsCell Culture TechniquesClinical Trials as TopicMalariaMalaria VaccinesAntimalarialsMalaria VaccinesBioreactorGood Manufacturing PracticeIn vitro cultivationMalariaPlasmodium falciparum

Identifiers

PMID30081913
PMCPMC6080485

What OpenQuestion holds

Textmetadata
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.