A clinically parameterized mathematical model of Shigella immunity to inform vaccine design Article Swipe
Courtney L. Davis
,
Rezwanul Wahid
,
Franklin R. Toapanta
,
Jakub K. Simon
,
Marcelo B. Sztein
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0189571
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0189571
We refine and clinically parameterize a mathematical model of the humoral immune response against Shigella, a diarrheal bacteria that infects 80-165 million people and kills an estimated 600,000 people worldwide each year. Using Latin hypercube sampling and Monte Carlo simulations for parameter estimation, we fit our model to human immune data from two Shigella EcSf2a-2 vaccine trials and a rechallenge study in which antibody and B-cell responses against Shigella's lipopolysaccharide (LPS) and O-membrane proteins (OMP) were recorded. The clinically grounded model is used to mathematically investigate which key immune mechanisms and bacterial targets confer immunity against Shigella and to predict which humoral immune components should be elicited to create a protective vaccine against Shigella. The model offers insight into why the EcSf2a-2 vaccine had low efficacy and demonstrates that at a group level a humoral immune response induced by EcSf2a-2 vaccine or wild-type challenge against Shigella's LPS or OMP does not appear sufficient for protection. That is, the model predicts an uncontrolled infection of gut epithelial cells that is present across all best-fit model parameterizations when fit to EcSf2a-2 vaccine or wild-type challenge data. Using sensitivity analysis, we explore which model parameter values must be altered to prevent the destructive epithelial invasion by Shigella bacteria and identify four key parameter groups as potential vaccine targets or immune correlates: 1) the rate that Shigella migrates into the lamina propria or epithelium, 2) the rate that memory B cells (BM) differentiate into antibody-secreting cells (ASC), 3) the rate at which antibodies are produced by activated ASC, and 4) the Shigella-specific BM carrying capacity. This paper underscores the need for a multifaceted approach in ongoing efforts to design an effective Shigella vaccine.
Related Topics
Concepts
Shigella
Immune system
Biology
Immunology
Microbiology
Shigellosis
Immunity
Virology
Salmonella
Bacteria
Genetics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pone.0189571
- https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0189571&type=printable
- OA Status
- gold
- Cited By
- 6
- References
- 60
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2782060096
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2782060096Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1371/journal.pone.0189571Digital Object Identifier
- Title
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A clinically parameterized mathematical model of Shigella immunity to inform vaccine designWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2018Year of publication
- Publication date
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2018-01-05Full publication date if available
- Authors
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Courtney L. Davis, Rezwanul Wahid, Franklin R. Toapanta, Jakub K. Simon, Marcelo B. SzteinList of authors in order
- Landing page
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https://doi.org/10.1371/journal.pone.0189571Publisher landing page
- PDF URL
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https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0189571&type=printableDirect link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0189571&type=printableDirect OA link when available
- Concepts
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Shigella, Immune system, Biology, Immunology, Microbiology, Shigellosis, Immunity, Virology, Salmonella, Bacteria, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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6Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1, 2020: 3, 2019: 1, 2018: 1Per-year citation counts (last 5 years)
- References (count)
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60Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7699999809265137 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.71670225 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |