ArticleProceedings of the National Academy of Sciences of the United States of America2010
Reactogenicity of live-attenuated Vibrio cholerae vaccines is dependent on flagellins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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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.
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.
Who cites it
44 citing papers in PubMed, 60 citations in OpenAlex.
- Safety and immunogenicity of PanChol, a single-dose live-attenuated oral cholera vaccine: results from a phase 1a, double-blind, randomised, placebo-controlled trial.The Lancet. Infectious diseases · 2026Trial
- Deployment of amBio · 2025Article
- Inflammation induced by the new lineage ofFrontiers in immunology · 2025Article
- Deployment of abioRxiv : the preprint server for biology · 2024Article
- The intersection between host-pathogen interactions and metabolism during Vibrio cholerae infection.Current opinion in microbiology · 2024Review
- Intestinal colonization againstAIMS microbiology · 2023Review
- DegS protease regulates the motility, chemotaxis, and colonization ofFrontiers in microbiology · 2023Article
- Article
- Vibrio cholerae Motility in Aquatic and Mucus-Mimicking Environments.Applied and environmental microbiology · 2021Article
- Identification of cholix toxin gene inIranian journal of microbiology · 2020Article
- Immunogenicity and protective efficacy of a live, oral cholera vaccine formulation stored outside-the-cold-chain for 140 days.BMC immunology · 2020Article
- Swimming motility of a gut bacterial symbiont promotes resistance to intestinal expulsion and enhances inflammation.PLoS biology · 2020Article
- Review
- Host-Microbe-Pathogen Interactions: A Review ofFrontiers in immunology · 2019Review
- Hypermutation-induced in vivo oxidative stress resistance enhances Vibrio cholerae host adaptation.PLoS pathogens · 2018Article
- A Critical Region in the FlaA Flagellin Facilitates Filament Formation of the Vibrio cholerae Flagellum.Journal of bacteriology · 2018Article
- A live vaccine rapidly protects against cholera in an infant rabbit model.Science translational medicine · 2018Article
- Tracking Vibrio cholerae Cell-Cell Interactions during Infection Reveals Bacterial Population Dynamics within Intestinal Microenvironments.Cell host & microbe · 2018Article
- Quantifying Vibrio cholerae Enterotoxicity in a Zebrafish Infection Model.Applied and environmental microbiology · 2017Article
- Plasma and Mucosal Immunoglobulin M, Immunoglobulin A, and Immunoglobulin G Responses to the Vibrio cholerae O1 Protein Immunome in Adults With Cholera in Bangladesh.The Journal of infectious diseases · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Cholera is a severe diarrheal disease caused by the motile Gram-negative rod Vibrio cholerae. Live-attenuated V. cholerae vaccines harboring deletions of the genes encoding cholera toxin have great promise for reducing the global burden of cholera. However, development of live vaccines has been hampered by the tendency of such strains to induce noncholeric reactogenic diarrhea in human subjects. The molecular bases of reactogenicity are unknown, but it has been speculated that reactogenic diarrhea is a response to V. cholerae's flagellum and/or the motility that it enables. Here, we used an infant rabbit model of reactogenicity to determine what V. cholerae factors trigger this response. We found that V. cholerae ctx mutants that produced flagellins induced diarrhea, regardless of whether the proteins were assembled into a flagellum or whether the flagellum was functional. In contrast, approximately 90% of rabbits infected with V. cholerae lacking all five flagellin-encoding genes did not develop diarrhea. Thus, flagellin production, independent of flagellum assembly or motility, is sufficient for reactogenicity. The intestinal colonization and intraintestinal localization of the nonreactogenic flagellin-deficient strain were indistinguishable from those of a flagellated motile strain; however, the flagellin-deficient strain stimulated fewer mRNA transcripts coding for proinflammatory cytokines in the intestine. Thus, reactogenic diarrhea may be a consequence of an innate host inflammatory response to V. cholerae flagellins. Our results suggest a simple genetic blueprint for engineering defined nonreactogenic live-attenuated V. cholerae vaccine strains.
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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.