Evidence map›Paper›PMID 21695140›Full record

Trial reportPloS one2011

Non-apical membrane antigen 1 (AMA1) IgGs from Malian children interfere with functional activity of AMA1 IgGs as judged by growth inhibition assay.

Kazutoyo Miura, Suwani Perera, Sarah Brockley, Hong Zhou, Joan A Aebig, Samuel E Moretz, Louis H Miller, Ogobara K Doumbo, Issaka Sagara, Alassane Dicko and 2 more

Open access · goldAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.9field-weighted citation impact, top 21% 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

10 citing papers in PubMed, 16 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Malaria vaccines and human immune responses.Current opinion in microbiology · 2016
    Review
  7. Review
  8. Article
  9. Review
  10. 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

12 authors at 3 institutions in 2 countries.

Kazutoyo MiuraLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Suwani Perera
Sarah Brockley
Hong Zhou
Joan A Aebig
Samuel E Moretz
Louis H Miller
Ogobara K Doumbo
Issaka Sagara
Alassane Dicko
Ruth D Ellis
Carole A Long
National Institute of Allergy and Infectious Diseases · USNational Institutes of Health · USUniversity of Bamako · ML

Funding

Mali International Center for Excellence in Research: Malaria Clinical ResearchZIAAI001056 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DUFFY, PATRICK · 2009 to 2024
$43.1M
Malaria Parasite Receptors And Host Cell LigandsZIAAI000241 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MILLER, LOUIS · 2009 to 2025
$15.3M
Host Immune Responses to Antigens of Malaria ParasitesZIAAI001020 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LONG, CAROLE · 2009 to 2025
$13.6M
Malaria Vaccine: AMA1-C1ZIAAI001001 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DUFFY, PATRICK · 2009 to 2012
$5.1M
Intramural NIH HHS
6 · The paper itself

Abstract

backgroundApical membrane antigen 1 (AMA1) is one of the best-studied blood-stage malaria vaccine candidates. When an AMA1 vaccine was tested in a malaria naïve population, it induced functionally active antibodies judged by Growth Inhibition Assay (GIA). However, the same vaccine failed to induce higher growth-inhibitory activity in adults living in a malaria endemic area. Vaccination did induce functionally active antibodies in malaria-exposed children with less than 20% inhibition in GIA at baseline, but not in children with more than that level of baseline inhibition.

methodsTotal IgGs were purified from plasmas collected from the pediatric trial before and after immunization and pools of total IgGs were made. Another set of total IgGs was purified from U.S. adults immunized with AMA1 (US-total IgG). From these total IgGs, AMA1-specific and non-AMA1 IgGs were affinity purified and the functional activity of these IgGs was evaluated by GIA. Competition ELISA was performed with the U.S.-total IgG and non-AMA1 IgGs from malaria-exposed children.

resultsAMA1-specific IgGs from malaria-exposed children and U.S. vaccinees showed similar growth-inhibitory activity at the same concentrations. When mixed with U.S.-total IgG, non-AMA1 IgGs from children showed an interference effect in GIA. Interestingly, the interference effect was higher with non-AMA1 IgGs from higher titer pools. The non-AMA1 IgGs did not compete with anti-AMA1 antibody in U.S.-total IgG in the competition ELISA.

conclusionChildren living in a malaria endemic area have a fraction of IgGs that interferes with the biological activity of anti-AMA1 antibody as judged by GIA. While the mechanism of interference is not resolved in this study, these results suggest it is not caused by direct competition between non-AMA1 IgG and AMA1 protein. This study indicates that anti-malaria IgGs induced by natural exposure may interfere with the biological effect of antibody induced by an AMA1-based vaccine in the target population.

Indexed as

AdolescentAdultAntibody SpecificityAntigens, ProtozoanChildHumansImmunizationImmunoglobulin GMalaria, FalciparumMalaria VaccinesMaliMembrane ProteinsMiddle AgedPlasmodium falciparumProtozoan ProteinsYoung AdultAntigens, Protozoanapical membrane antigen I, PlasmodiumImmunoglobulin GMalaria VaccinesMembrane ProteinsProtozoan Proteins

Identifiers

PMID21695140
PMCPMC3113848
OpenAlexW2021540724

What OpenQuestion holds

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LicenceCC0
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.