Evidence map›Paper›PMID 31206156›Full record

ArticleGlycobiology2019

Characterization and immunogenicity of a Shigella flexneri 2a O-antigen bioconjugate vaccine candidate.

Neil Ravenscroft, Martin Braun, Joerg Schneider, Anita M Dreyer, Michael Wetter, Micha A Haeuptle, Stefan Kemmler, Michael Steffen, Dominique Sirena, Stefan Herwig and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Glycobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

28 citing papers in PubMed, 43 citations in OpenAlex.

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  20. Incidence of AsymptomaticLife (Basel, Switzerland) · 2022
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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

15 authors at 3 institutions in 3 countries.

Neil RavenscroftDepartment of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
Martin BraunLimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.
Joerg SchneiderLimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.
Anita M DreyerLimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.
Michael WetterLimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.
Micha A HaeuptleLimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.
Stefan KemmlerLimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.
Michael SteffenLimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.
Dominique SirenaLimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.
Stefan HerwigLimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.
Paula CarranzaLimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.
Claire JonesDepartment of Paediatrics, University of Oxford, Oxford OX3 9DU, United Kingdom.
Andrew J PollardDepartment of Paediatrics, University of Oxford, Oxford OX3 9DU, United Kingdom.
Michael WackerLimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.
Michael KowarikLimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.
Spital Limmattal · CHUniversity of Oxford · GBUniversity of Cape Town · ZA

Funding

Wellcome TrustWellcome Trust 100527
6 · The paper itself

Abstract

Shigellosis remains a major cause of diarrheal disease in developing countries and causes substantial morbidity and mortality in children. Vaccination represents a promising preventive measure to fight the burden of the disease, but despite enormous efforts, an efficacious vaccine is not available to date. The use of an innovative biosynthetic Escherichia coli glycosylation system substantially simplifies the production of a multivalent conjugate vaccine to prevent shigellosis. This bioconjugation approach has been used to produce the Shigella dysenteriae type O1 conjugate that has been successfully tested in a phase I clinical study in humans. In this report, we describe a similar approach for the production of an additional serotype required for a broadly protective shigellosis vaccine candidate. The Shigella flexneri 2a O-polysaccharide is conjugated to introduced asparagine residues of the carrier protein exotoxin A (EPA) from Pseudomonas aeruginosa by co-expression with the PglB oligosaccharyltransferase. The bioconjugate was purified, characterized using physicochemical methods and subjected to preclinical evaluation in rats. The bioconjugate elicited functional antibodies as shown by a bactericidal assay for S. flexneri 2a. This study confirms the applicability of bioconjugation for the S. flexneri 2a O-antigen, which provides an intrinsic advantage over chemical conjugates due to the simplicity of a single production step and ease of characterization of the homogenous monomeric conjugate formed. In addition, it shows that bioconjugates are able to raise functional antibodies against the polysaccharide antigen.

Indexed as

AnimalsFemaleImmunogenicity, VaccineO AntigensRatsRats, Sprague-DawleyShigella flexneriVaccines, ConjugateO AntigensVaccines, Conjugatebiosynthetic glycoconjugate vaccineEscherichia coli glycosylationfunctional antibodiesimmunogenicityShigella flexneri 2a

Identifiers

PMID31206156
PMCPMC6704370
OpenAlexW2949873935

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.