Evidence map›Paper›PMID 27188716›Full record

ArticleMalaria journal2016

Analysis of the dose-dependent stage-specific in vitro efficacy of a multi-stage malaria vaccine candidate cocktail.

Alexander Boes, Holger Spiegel, Robin Kastilan, Susanne Bethke, Nadja Voepel, Ivana Chudobová, Judith M Bolscher, Koen J Dechering, Rolf Fendel, Johannes F Buyel and 3 more

Abstract read
In one paragraph

Article in Malaria journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Antimalarial cytoskeletal targeting with broad apicomplexan activity.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. TheThe Journal of biological chemistry · 2020
    Article
  8. AFrontiers in cellular and infection microbiology · 2019
    Article
  9. Functional antibodies againstWellcome open research · 2018
    Article
  10. Article
  11. Review
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

13 authors.

Alexander BoesFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Holger SpiegelFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany. holger.spiegel@ime.fraunhofer.de.
Robin KastilanFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Susanne BethkeFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Nadja VoepelFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Ivana ChudobováFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Judith M BolscherTropIQ Health Science, Geert Grooteplein 28, Huispost 268, 6525, GA, Nijmegen, The Netherlands.
Koen J DecheringTropIQ Health Science, Geert Grooteplein 28, Huispost 268, 6525, GA, Nijmegen, The Netherlands.
Rolf FendelFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Johannes F BuyelFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Andreas ReimannFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Stefan SchillbergFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Rainer FischerFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe high incidence and mortality rate of malaria remains a serious burden for many developing countries, and a vaccine that induces durable and highly effective immune responses is, therefore, desirable. An earlier analysis of the stage-specific in vitro efficacy of a malaria vaccine candidate cocktail (VAMAX) considered the general properties of complex multi-component, multi-stage combination vaccines in rabbit immunization experiments using a hyper-immunization protocol featuring six consecutive boosts and a strong, lipopolysaccharide-based adjuvant. This follow-up study investigates the effect of antigen dose on the in vitro efficacy of the malaria vaccine cocktail using a conventional vaccination scheme (one prime and two boosts) and a human-compatible adjuvant (Alhydrogel(®)).

resultsIgG purified from rabbits immunized with 0.1, 1, 10 or 50 µg doses of the VAMAX vaccine candidate cocktail was analysed for total IgG and antigen-cocktail-specific titers. An increase in cocktail-specific titers was observed between 0.1 and 1 µg and between 10 and 50 µg, whereas no significant difference in titers was observed between 1 and 10 µg. Antigen component-specific antibody titers and stage-specific in vitro efficacy assays were performed with pooled IgG from animals immunized with 1 and 50 µg of the VAMAX cocktail. Here, the component-specific antibody levels showed clear dose dependency whereas the determined stage-specific in vitro IC50 values (as a correlate of efficacy) were only dependent on the titer amounts of stage-specific antibodies.

conclusionsThe stage-specific in vitro efficacy of the VAMAX cocktail strongly correlates with the corresponding antigen-specific titers, which for their part depend on the antigen dose, but there is no indication that the dose has an effect on the in vitro efficacy of the induced antibodies. A comparison of these results with those obtained in the previous hyper-immunization study (where higher levels of antigen-specific IgG were observed) suggests that there is a significant need to induce an immune response matching efficacy requirements, especially for a PfAMA1-based blood stage vaccine, by using higher doses, better adjuvants and/or better formulations.

Indexed as

Immunization ScheduleAdjuvants, ImmunologicAluminum HydroxideAnimalsAntibodies, ProtozoanDose-Response Relationship, ImmunologicFollow-Up StudiesImmunoglobulin GMalaria VaccinesRabbitsAdjuvants, ImmunologicAluminum HydroxideAntibodies, ProtozoanImmunoglobulin GMalaria VaccinesCalibration-free concentration analysis (CFCA)Combination vaccinePichia pastorisPlasmodium falciparum

Identifiers

PMID27188716
PMCPMC4869186

What OpenQuestion holds

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LicenceCC BY
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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.