Evidence map›Paper›PMID 31160100›Full record

ArticleVaccine2019

O-acetylation of typhoid capsular polysaccharide confers polysaccharide rigidity and immunodominance by masking additional epitopes.

Krisztina Hitri, Michelle M Kuttel, Gianluigi De Benedetto, Kay Lockyer, Fang Gao, Peter Hansal, Timothy R Rudd, Emma Beamish, Sjoerd Rijpkema, Neil Ravenscroft and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Vaccine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

14 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Prophage-Derived Regions inInternational journal of molecular sciences · 2023
    Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Science immunology · 2021
    Article
  12. Article
  13. Glycoconjugate vaccines againstBiophysical reviews · 2021
    Review
  14. Molecules (Basel, Switzerland) · 2020
    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

11 authors at 2 institutions in 2 countries.

Krisztina HitriDivision of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
Michelle M KuttelDepartment of Computer Science, University of Cape Town, Private Bag X3, Rondebosch, 7701 Cape Town, South Africa.
Gianluigi De BenedettoDivision of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
Kay LockyerDivision of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
Fang GaoDivision of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
Peter HansalDivision of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
Timothy R RuddLaboratory of Molecular Structure, Analytical and Biological Sciences, NIBSC, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
Emma BeamishDivision of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
Sjoerd RijpkemaDivision of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
Neil RavenscroftDepartment of Chemistry, University of Cape Town, Private Bag X3, Rondebosch, 7701 Cape Town, South Africa.
Barbara BolgianoDivision of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK. Electronic address: Barbara.Bolgiano@nibsc.org.
National Institute for Biological Standards and Control · GBUniversity of Cape Town · ZA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In this work, we explore the effects of O-acetylation on the physical and immunological characteristics of the WHO International Standards of Vi polysaccharide (Vi) from both Citrobacter freundii and Salmonella enterica serovar Typhi. We find that, although structurally identical according to NMR, the two Vi standards have differences with respect to susceptibility to de-O-acetylation and viscosity in water. Vi standards from both species have equivalent mass and O-acetylation-dependent binding to a mouse monoclonal antibody and to anti-Vi polyclonal antisera, including the WHO International Standard for human anti-typhoid capsular Vi PS IgG. This study also confirms that human anti-Vi sera binds to completely de-O-acetylated Vi. Molecular dynamics simulations provide conformational rationales for the known effect of de-O-acetylation both on the viscosity and antigenicity of the Vi, demonstrating that de-O-acetylation has a very marked effect on the conformation and dynamic behavior of the Vi, changing the capsular polysaccharide from a rigid helix into a more flexible coil, as well as enhancing the strong interaction of the polysaccharide with sodium ions. Partial de-O-acetylation of Vi revealed hidden epitopes that were recognized by human and sheep anti-Vi PS immune sera. These findings have significance for the manufacture and evaluation of Vi vaccines.

Indexed as

AcetylationAntibodies, BacterialCitrobacter freundiiHumansImmune SeraImmunodominant EpitopesMolecular Dynamics SimulationPolysaccharides, BacterialSalmonella typhiTyphoid FeverTyphoid-Paratyphoid VaccinesWorld Health OrganizationAntibodies, BacterialImmune SeraImmunodominant EpitopesPolysaccharides, BacterialTyphoid-Paratyphoid VaccinesEntericGlycoconjugateMolecular modellingNuclear magnetic resonanceVaccineVi polysaccharide

Identifiers

PMID31160100
PMCPMC6997886
OpenAlexW2947542850

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.