Evidence map›Paper›PMID 33430886›Full record

ArticleMalaria journal2021

Isolation and light chain shuffling of a Plasmodium falciparum AMA1-specific human monoclonal antibody with growth inhibitory activity.

Melanie Seidel-Greven, Otchere Addai-Mensah, Holger Spiegel, Gwladys Nina Chiegoua Dipah, Stefan Schmitz, Gudrun Breuer, Margaret Frempong, Andreas Reimann, Torsten Klockenbring, Rainer Fischer and 2 more

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2021. 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
1.2field-weighted citation impact, top 22% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Malaria: past, present, and future.Signal transduction and targeted therapy · 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

12 authors at 4 institutions in 4 countries.

Melanie Seidel-GrevenFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstr.6, 52074, Aachen, Germany.
Otchere Addai-MensahFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstr.6, 52074, Aachen, Germany.
Holger SpiegelFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstr.6, 52074, Aachen, Germany.
Gwladys Nina Chiegoua DipahFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstr.6, 52074, Aachen, Germany.
Stefan SchmitzFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstr.6, 52074, Aachen, Germany.
Gudrun BreuerFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstr.6, 52074, Aachen, Germany.
Margaret FrempongDepartment of Molecular Medicine, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Andreas ReimannFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstr.6, 52074, Aachen, Germany.
Torsten KlockenbringFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstr.6, 52074, Aachen, Germany.
Rainer FischerFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstr.6, 52074, Aachen, Germany.
Stefan BarthFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstr.6, 52074, Aachen, Germany.
Rolf FendelFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstr.6, 52074, Aachen, Germany. rolf.fendel@uni-tuebingen.de.ORCID http://orcid.org/0000-0003-4716-0311
Fraunhofer Institute for Molecular Biology and Applied Ecology · DEKwame Nkrumah University of Science and Technology · GHPurdue University West Lafayette · USSouth African Medical Research Council · ZA

Funding

Fraunhofer-Gesellschaft -
6 · The paper itself

Abstract

backgroundPlasmodium falciparum, the parasite causing malaria, affects populations in many endemic countries threatening mainly individuals with low malaria immunity, especially children. Despite the approval of the first malaria vaccine Mosquirix™ and very promising data using cryopreserved P. falciparum sporozoites (PfSPZ), further research is needed to elucidate the mechanisms of humoral immunity for the development of next-generation vaccines and alternative malaria therapies including antibody therapy. A high prevalence of antibodies against AMA1 in immune individuals has made this antigen one of the major blood-stage vaccine candidates. MATERIAL AND

methodsUsing antibody phage display, an AMA1-specific growth inhibitory human monoclonal antibody from a malaria-immune Fab library using a set of three AMA1 diversity covering variants (DiCo 1-3), which represents a wide range of AMA1 antigen sequences, was selected. The functionality of the selected clone was tested in vitro using a growth inhibition assay with P. falciparum strain 3D7. To potentially improve affinity and functional activity of the isolated antibody, a phage display mediated light chain shuffling was employed. The parental light chain was replaced with a light chain repertoire derived from the same population of human V genes, these selected antibodies were tested in binding tests and in functionality assays.

resultsThe selected parental antibody achieved a 50% effective concentration (EC

conclusionWe have thus shown that a compact immune human phage display library is sufficient for the isolation of potent inhibitory monoclonal antibodies and that minor sequence mutations dramatically increase expression levels in Nicotiana benthamiana. Interestingly, the antibody blocks parasite inhibition independently of binding to RON2, thus having a yet undescribed mode of action.

Indexed as

Immunity, HumoralAntibodies, MonoclonalAntibodies, ProtozoanAntigens, ProtozoanHumansMalaria VaccinesMembrane ProteinsPlasmodium falciparumProtozoan ProteinsAntibodies, MonoclonalAntibodies, ProtozoanAntigens, Protozoanapical membrane antigen I, PlasmodiumMalaria VaccinesMembrane ProteinsProtozoan ProteinsApical membrane antigen 1Chain shufflingHuman monoclonal antibodiesMalariaParasite growth inhibitionPhage displayPlant expressionPlasmodium falciparum

Identifiers

PMID33430886
PMCPMC7798374
OpenAlexW3118825163

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.