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Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
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Developing and utilizing controlled human models of infection.

Chad K Porter1, A Louis Bourgeois2, Robert W Frenck3

  • 1Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States.

Vaccine
|June 7, 2017
PubMed
Summary
This summary is machine-generated.

Controlled human infection models (CHIMs) show promise for accelerating Shigella and enterotoxigenic Escherichia coli (ETEC) vaccine development. Further standardization and research are needed to optimize CHIMs and address host-pathogen interactions for reliable results.

Keywords:
ChallengeControlled human infection modelETECEnterotoxigenic Escherichia coliShigella

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Area of Science:

  • Infectious Diseases
  • Vaccinology
  • Microbiology

Background:

  • Controlled human infection models (CHIMs) offer unique advantages for evaluating vaccine efficacy against enteric pathogens like Shigella and enterotoxigenic Escherichia coli (ETEC).
  • Despite growing interest, optimal integration and maximization of CHIMs in vaccine development pipelines require further clarification.

Purpose of the Study:

  • To explore and define best practices for utilizing CHIMs in Shigella and ETEC vaccine development through a focused workshop.
  • To identify key areas for improvement in clinical outcomes, nonclinical assessments, and model standardization within CHIMs.

Main Methods:

  • A workshop utilizing the World Café method was conducted as part of the Vaccines Against Shigella and ETEC (VASE) Conference.
  • Discussions were structured around clinical outcomes, nonclinical outcomes, and model standardization, involving researchers with diverse expertise.

Main Results:

  • Key discussion points included the need for harmonized clinical endpoint definitions, optimized attack rates, improved sample collection methods, and development of non-stool based endpoints.
  • Nonclinical discussions highlighted the potential of omics-based approaches, host predictors of susceptibility, and novel immune response characterizations.
  • Model standardization discussions emphasized the value of shared institutional procedures for various CHIM aspects, from endpoint assessment to subject selection.

Conclusions:

  • CHIMs hold significant potential to accelerate the development of Shigella and ETEC vaccines.
  • Variability within CHIMs and incomplete understanding of host-pathogen interactions necessitate careful consideration to avoid negatively impacting promising vaccine candidates.
  • Future workshops are essential to ensure the optimal and standardized application of CHIMs in vaccine development.