In vitro / in vivo
models

Non-invasive longitudinal monitoring of pathogen-host interactions and therapies using in vivo imaging

Mouse model to assess microbiota impact

In vitro cellular systems mimicking the relevant micro-environment for host – microbe interaction investigation and for immune response assessment

In vitro / in vivo models

From relevant in vitro model engineering to in vivo validated models: de-risking and accelerating your product development

In vitro screening of drug candidates for their anti-infectious or probiotic activities:

  • In vitro studies using standard microbiological approaches,
  • In vitro cellular systems mimicking the relevant micro-environment for the assessment of immune responses and host-microbe interactions.

In vivo evaluation of the efficacy of drug candidates with respect to their anti-infectious or probiotic activities using preclinical models:

  • Invasive in vivo models,
  • Non-invasive longitudinal monitoring of pathogen-host interactions and therapies using in vivo imaging,
  • Gnotobiotic mouse models to assess the influence of the microbiota.

Preclinical studies performed in vitro, in vivo, and ex vivo contribute to the evaluation of the efficacy of a drug candidate and provide insights into the mechanisms of action involved. Hence, they contribute to the prediction and better understanding of the translational implications of risk factors and the efficacy of anti-infective and/or probiotic candidates. The identification of preclinical models that mimic human physiology/pathology remains a challenge and a major priority.

Gaps in our knowledge still exist, and further development is needed or ongoing, with the aims of:

  • ­accelerating drug discovery by candidate pre-selection through the deployment of in vitro systems mimicking the physiological function or disease microenvironment,
  • ­providing animal-free toxicity assays by developing cost effective and controlled in vitro tools that are capable of defining predictive and relevant safety signals,
  • ­ultimately validating the drug candidate using established preclinical models or developing new models aligned with the 3R principles (replacement, reduction, and refinement) whenever possible.

Within this framework, we focus on developing and customizing predictive translational models.

1

In vitro screening of drug candidates for their anti-infective or probiotic activities
In vitro studies using standard microbiological approaches

To screen for potential anti-infective or probiotic activity among several candidates prior to preclinical and/or clinical studies (de-risking), we deploy standard microbiological screening technologies/tests that can be performed under anaerobic or aerobic conditions with BSL-2 and BSL-3 organisms of interest. We can help you to preselect the top/optimal candidate(s) on the basis of several technologies/readouts:

  • MIC-based methods,
  • antivirus testing: EC50, pre- and post- infection models, neutralization assay, immunofluorescence,
  • timed killing assays using standard and/or alternative media mimicking the cytotoxicity of pathological or physiological environments,
  • phage activity against clinical isolates,
  • biofilm formation and eradication assays using standard (MBEC, Bioflux) and innovative (BiofilmCare) technologies.

To learn more about MICRO web, anoxic platform, biofilm ID, and BiofilmCare, go to our case study: ATOM.

2

The use of in vitro cellular systems mimicking the relevant micro-environment for the study of immune responses and host–microbe interactions

To reproduce specific properties, allowing a direct assessment of cell and tissue function, we use “standard” co-culture methods, as well as newly developed organs-on-a-chip, i.e. biomimetic tissue constructs containing microfluidic chip systems, designed to advance your drug development within the context of precision medicine. Our current capabilities include:

  • intestinal micro-environment: to evaluate the effectiveness of pre-/ post-/ pro-biotic therapeutic and preventive strategies, taking into account the influences of the gut microbiota, intestinal epithelium, and host immune response:
    • transwell-based co-culture systems, in which intestinal epithelial cells grown on membrane separate immune cells from orally delivered therapeutics of interest,
    • Gut-on-a-chip to mimic the gut microenvironment under shear stress, in which intestinal epithelial cells and a natural extracellular matrix separate the “lumen” of the intestine from circulating blood leukocytes.
  • Blood-on-a-chip technology to emulate the initial steps of the vaccine response, which is key to the definition of the final immune status.

These technologies allow us to generate pertinent biological information, supported by actionable data and documentation, to ensure the progression of your research from discovery to product development.

3

In vivo evaluation of the efficacy of drug candidates with respect to their anti-infective or probiotic activity using preclinical models
Invasive in vivo models

You seek a cost-effective, robust methodology that will deliver actionable results from bacterial/viral infection models for either classical (drug or vaccine) or alternative emerging (natural products/extracts, phage therapy) therapies.
We can:

  • ­identify and source relevant clinical isolates, characterize strains, and use selected relevant clinical pathogens in the most suitable model,
  • ­establish/customize in vivo models that mimic clinical infection with respect to:
    • routes of infection: IN, IV, or SC,
    • induced infections: UTI, bacteremia, or pneumonia.
  • ­assess pathogen biodistribution over time and identify target organs: biodistribution, PK,
  • ­evaluate treatment efficacy (CFU, PFU, or ED50),
  • ­integrate the complex data generated from multiple source.

4

Non-invasive longitudinal monitoring of pathogen-host interactions and therapies using in vivo imaging

The evolution of imaging technologies now permits preclinical longitudinal studies to be performed within the same animal during the infection, which significantly increases the quality and quantity of information available.

We can deploy multimodality imaging to permit the simultaneous monitoring of several parameters within the same animal (e.g., the dissemination of infection and host immune response), which can significantly reduce the number of animals required to yield statistically meaningful data.

We can deploy Biophotonic imaging (BPI) technologies in the context of pathogenic events or the establishment of a pharmacological profile, which can improve established models and increase the number of readouts
Example applications include:

  • ­longitudinal monitoring of infection: study of the temporal and spatial (tomography) progression or regression of a pathogen,
  • ­in vivo monitoring of the host immune response,
  • ­biodistribution of labelled drug analogs and microorganisms,
  • ­in vivo pharmacological monitoring.

To learn more about infectious disease using in vivo models, read our case study Mosaic.

5

Gnotobiotic mouse models to assess the influence of the microbiota

To assess influences of the microbiota on health and diseases, to identify and select the key active components, or to assess the effect of drugs on its integrity, we have developed a gnotobiotic mouse model.

We can:

  • evaluate antimicrobial effects (dysbiosis) and resistance, as well as the effects of drugs on commensals and intestinal barrier function using a standardized mouse model (GM15), which comprises 15 bacterial strains that are representative of the most prevalent bacterial taxa in the mouse fecal microbiota,
  • provide a reproducible mouse model to aid understanding of the role of the gut microbiota in the prevention, induction, or treatment of diseases,
  • use the model as a surrogate to establish customized and more complex consortia in order to investigate specific biological questions.

These technologies allow us to generate pertinent biological information, supported by actionable data and documentation, that ensure the progression of your research from discovery to product development.

Learn more about it in our case study GM 15 mouse model.

2

The use of in vitro cellular systems mimicking the relevant micro-environment for the study of immune responses and host–microbe interactions

To reproduce specific properties, allowing a direct assessment of cell and tissue function, we use “standard” co-culture methods, as well as newly developed organs-on-a-chip, i.e. biomimetic tissue constructs containing microfluidic chip systems, designed to advance your drug development within the context of precision medicine. Our current capabilities include:

  • intestinal micro-environment: to evaluate the effectiveness of pre-/ post-/ pro-biotic therapeutic and preventive strategies, taking into account the influences of the gut microbiota, intestinal epithelium, and host immune response:
    • transwell-based co-culture systems, in which intestinal epithelial cells grown on membrane separate immune cells from orally delivered therapeutics of interest,
    • Gut-on-a-chip to mimic the gut microenvironment under shear stress, in which intestinal epithelial cells and a natural extracellular matrix separate the “lumen” of the intestine from circulating blood leukocytes.
  • Blood-on-a-chip technology to emulate the initial steps of the vaccine response, which is key to the definition of the final immune status.

These technologies allow us to generate pertinent biological information, supported by actionable data and documentation, to ensure the progression of your research from discovery to product development.

4

Non-invasive longitudinal monitoring of pathogen-host interactions and therapies using in vivo imaging

The evolution of imaging technologies now permits preclinical longitudinal studies to be performed within the same animal during the infection, which significantly increases the quality and quantity of information available.

We can deploy multimodality imaging to permit the simultaneous monitoring of several parameters within the same animal (e.g., the dissemination of infection and host immune response), which can significantly reduce the number of animals required to yield statistically meaningful data.

We can deploy Biophotonic imaging (BPI) technologies in the context of pathogenic events or the establishment of a pharmacological profile, which can improve established models and increase the number of readouts
Example applications include:

  • ­longitudinal monitoring of infection: study of the temporal and spatial (tomography) progression or regression of a pathogen,
  • ­in vivo monitoring of the host immune response,
  • ­biodistribution of labelled drug analogs and microorganisms,
  • ­in vivo pharmacological monitoring.

To learn more about infectious disease using in vivo models, read our case study Mosaic.

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