Evidence map›Paper›PMID 33813141›Full record

ArticleEBioMedicine2021

Immune response characterization in a human challenge study with a Shigella flexneri 2a bioconjugate vaccine.

Kristen A Clarkson, Kawsar R Talaat, Cristina Alaimo, Patricia Martin, A Louis Bourgeois, Anita Dreyer, Chad K Porter, Subhra Chakraborty, Jessica Brubaker, Daniel Elwood and 9 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06615375 (Phase 2b, Double-blind, Placebo-controlled Efficacy Challenge Study With the Shigella Tetravalent Bioconjugate Vaccine Shigella4V2), which is not on this map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
8.4field-weighted citation impact, top 2% 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.

NCT06615375 phase2active not recruitingnot on this mapstarted 2024, after this paper: background citation

Phase 2b, Double-blind, Placebo-controlled Efficacy Challenge Study With the Shigella Tetravalent Bioconjugate Vaccine Shigella4V2

TypeinterventionalSponsorLimmaTech Biologics AGRan2024 to 2026Enrolled120ConditionsShigellosisArmsShigella4V2, Placebo
3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 47 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. Review
  8. Review
  9. Development of a Novel mRNA Vaccine AgainstBioinformatics and biology insights · 2025
    Article
  10. Article
  11. Article
  12. Exploring Natural Immune Responses toOpen forum infectious diseases · 2024
    Article
  13. Oral immunization withmSphere · 2024
    Article
  14. Review
  15. Article
  16. Shigella-Controlled Human Infection Models: Current and Future Perspectives.Current topics in microbiology and immunology · 2024
    Review
  17. Article
  18. Development of themSphere · 2023
    Article
  19. A NovelmSphere · 2023
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 2 countries.

Kristen A ClarksonDepartment of Enteric Infections, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
Kawsar R TalaatDepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Cristina AlaimoLimmaTech Biologics AG, Schlieren, Switzerland.
Patricia MartinLimmaTech Biologics AG, Schlieren, Switzerland.
A Louis BourgeoisPATH, Washington, DC, United States.
Anita DreyerLimmaTech Biologics AG, Schlieren, Switzerland.
Chad K PorterNaval Medical Research Center, Silver Spring, MD, United States.
Subhra ChakrabortyDepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Jessica BrubakerDepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Daniel ElwoodDepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Rahel FrölichLimmaTech Biologics AG, Schlieren, Switzerland.
Barbara DeNearingDepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Hailey P WeertsDepartment of Enteric Infections, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
Brittany FeijooDepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Jane HalpernDepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
David SackDepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Mark S RiddleNaval Medical Research Center, Silver Spring, MD, United States.
Veronica Gambillara FonckLimmaTech Biologics AG, Schlieren, Switzerland.
Robert W KaminskiDepartment of Enteric Infections, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States. Electronic address: Robert.W.Kaminski.civ@mail.mil.
Johns Hopkins University · USSpital Limmattal · CHWalter Reed Army Institute of Research · USNaval Medical Research Command · USProgram for Appropriate Technology in Health · US

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundDiarrheal diseases are a leading cause of global morbidity and mortality affecting all ages, but especially children under the age of five in resource-limited settings. Shigella is a leading contributor to diarrheal diseases caused by bacterial pathogens and is considered a significant antimicrobial resistance threat. While improvements in hygiene, and access to clean water help as control measures, vaccination remains one of the most viable options for significantly reducing morbidity and mortality.

methodsFlexyn2a is a bioconjugate vaccine manufactured using novel conjugation methodologies enzymatically linking the O-polysaccharide of S. flexneri 2a to exotoxin A of Pseudomonas aeruginosa. The protective capacity of Flexyn2a was assessed in a controlled human infection model after two intramuscular immunizations. Immune responses pre- and post-immunization and/or infection were investigated and are described here.

findingsFlexyn2a induced lipopolysaccharide (LPS)-specific serum IgG responses post-immunization which were associated with protection against shigellosis. Additionally, several other immune parameters, including memory B cell responses, bactericidal antibodies and serum IgA, were also elevated in vaccinees protected against shigellosis. Immunization with Flexyn2a also induced gut-homing, LPS-specific IgG and IgA secreting B cells, indicating the vaccine induced immune effectors functioning at the site of intestinal infection.

interpretationCollectively, the results of these immunological investigations provide insights into protective immune mechanisms post-immunization with Flexyn2a which can be used to further guide vaccine development and may have applicability to the larger Shigella vaccine field.

fundingFunding for this study was provided through a Wellcome Trust grant.

Indexed as

ImmunityAntibodies, BacterialAntibody SpecificityDysentery, BacillaryHumansImmunoglobulin AImmunoglobulin GImmunoglobulin MImmunologic MemoryLipopolysaccharidesLymphocytesShigella flexneriShigella VaccinesVaccinationAntibodies, BacterialImmunoglobulin AImmunoglobulin GImmunoglobulin MLipopolysaccharidesShigella VaccinesBioconjugate vaccineGut-homing responsesHuman challengeImmunogenicityParenteral immunizationShigella

Identifiers

PMID33813141
PMCPMC8047506
OpenAlexW3141607672

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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.