Respiratory diseases

Respiratory diseases include chronic respiratory diseases (COPD, asthma, pulmonary hypertension) and respiratory infections due to communicable infectious diseases (upper respiratory tract infections and lower respiratory tract infections). These pathologies affect the airways, bronchial tubes and lungs. According to the WHO, respiratory diseases are among the leading causes of death worldwide. Lung infections (mostly pneumonia and tuberculosis), lung cancer and chronic obstructive pulmonary disease (COPD) together accounted for more than 9 million deaths worldwide in 2008.

The Non-Human Primate model is a model of choice for the assessment of the efficacy or safety of drugs developed in respiratory diseases. As NHP share similarity with humans in physiology, anatomy (vertical posture, nasal cavity similar to that of human children), and immune system, it is a well-suited in vivo model for exploratory, respiratory toxicity and efficacy studies.

Cynbiose and Cynbiose Respiratory have built an extensive expertise in this particular therapeutic area from early exploratory studies (both in vitro and in vivo), to predictive Proof-of-Concept models. Moreover, we have unparalleled capabilities for the in vitro and in vivo assessment of aerosol therapies.

 

Dedicated solution for inhaled products & aerosoltherapies
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Efficacy studies
  • SARS-CoV-2 / COVID-19 model
  • Lung inflammation
  • Respiratory viral infections: hMPV, hRSV, measles, SARS-CoV-2
  • On-demand preclinical models: contact us to discuss your needs
Exploratory studies
  • In vitro assays for aerosol therapies
  • Pharmacokinetics including pulmonary PK
  • Nasal and pulmonary biodistribution
  • Pharmacodynamics
  • Early toxicology studies

SARS-CoV-2 / COVID-19 model

Cynbiose can assess the efficacy of your therapeutics or vaccine in a translational non-human primate (NHP) model. This model is relevant to test innovative or repurposed drug candidates as well as aerosoltherapies.

Species

  • Cynomolgus macaque (Macaca fascicularis)
  • African green monkey (genus Chlorocebus)

Pathogen

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) / COVID-19 strains (Primary strain, various European D614G variants, UK variant,  South-African variant, Brazilian variant, Delta variant, Omicron original and BA5 subvariant)
  • Infection method : intratracheal, intranasal pulverization

Type of test item

  • Vaccines
  • Antibodies, immunotherapies, antiviral candidates, small molecules
  • Combined treatments
  • Aerosoltherapies & inhaled products

Objectives

  • Efficacy assessment of vaccines or therapeutics
  • Evaluation of systemic or topical (incl nebulization) administrations

Read-outs

  • Clinical follow-up
  • Core body temperature : continuous monitoring using an implantable data logger
  • Clinical pathology : biochemistry and complete blood count with differential) in a BSL1/2/3 setting thanks to state-of-the-art biological analyzers
  • Sampling : Bronchoalveolar lavage, Nasal & nasopharyngeal swabs, blood sampling, feces
  • Immunomonitoring
  • Viral detection and quantification by RT-qPCR
  • Viral titration using  using the Median Tissue Culture Infectious Dose (TCID50) assay
  • Assessment of the host response by seroneutralization assays
  • Histopathology
  • Custom readouts & biomarkers

Scientific publications

  • Preclinical efficacy, safety and immunogenicity assessment of a vaccine candidate in a cynomolgus monkey model of SARS-CoV-2 infection.
    Confais J, Toussenot M, Ployart S, Bech-Sabat G, Roca M, Pizzorno A, Julien T, Rosa-Calatrava M, March R, Contamin H.
    Festival of Biologics, Nov 2-4, 2022 & Immunotherapies & Innovations for Infectious Diseases congress, November 23-24, 2022.
  • Preclinical efficacy, safety, and immunogenicity in cynomolgus macaques of the PHH-1V COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2.
    Moros A, Fernández A, Bech-Sabat G, Barreiro A, Garriga C, Pradenas E, Marfil S, Blanco J, Sisteré M, Meyerhans A, Confais J, Toussenot M, Contamin H, Pizzorno A, Rosa-Calatrava M, Prat T, Roca M, March R, Prenafeta A, Ferrer L.
    Spanish Society for Virology national congress, Sept 6-9, 2022.
  • African Green Monkey model of SARS-CoV-2 infection shows mild lung pathology and viral replication in the airways.
    Confais J, Toussenot M, Julien T, Ployart S, Pizzorno A, Rosa-Calatrava M, Contamin H.
    Immunotherapies & Innovations for Infectious Diseases congress, 9-10th December, 2020.

Scientific partners

  • VirPath laboratory (Claude Bernard Lyon University, INSERM, CNRS, ENS Lyon) specializing in virology and human respiratory pathologies
  •  VirNext is a spin-off (EZUS Lyon) of the Université Claude Bernard Lyon 1 (UCBL1), which was created within the VirPath laboratory to foster industrial partnerships and enhance translational research. VirNext offers expertise in the field of respiratory viruses (including SARS-CoV-2) and provides a large panel of technologies, including egg and cell-based processes of virus and vaccine antigen production, and several potency tests using in vitro (cell lines and reconstituted human airway epithelium) and in vivo models of infections dedicated to the evaluation of prophylactic and therapeutic candidates.

Lung inflammation

A non-human primate inflammation model using LPS.

 

For more information, please contact Cynbiose Respiratory.

Respiratory viral infections: hMPV, hRSV, measles, SARS-CoV-2

Species

  • Cynomolgus macaque (Macaca fascicularis)
  • Rhesus macaque (Macaca mulatta)
  • African green monkey (genus Chlorocebus)

Pathogens

Infection method : Intratracheal microspray, intranasal

Objectives

  • Infection tropism
  • Efficacy assessment of vaccines or therapeutics
  • Evaluation of systemic or topical (incl nebulization) administrations

Readouts

  • Clinical follow-up
  • Core body temperature : continuous monitoring using an implantable data logger
  • Clinical pathology : biochemistry and complete blood count with differential) in a BSL1/2/3 setting thanks to state-of-the-art biological analyzers
  • Bronchoalveolar lavage
  • Nasal & nasopharyngeal swabs
  • Immunomonitoring
  • Viral detection and quantification by RT-qPCR
  • Viral titration using  using the Median Tissue Culture Infectious Dose (TCID50) assay
  • Assessment of the host response by seroneutralization assays
  • Histopathology
  • Custom readouts

Scientific publications

  • African Green Monkey model of SARS-CoV-2 infection shows mild lung pathology and viral replication in the airways.
    Confais J, Toussenot M, Julien T, Ployart S, Pizzorno A, Rosa-Calatrava M, Contamin H.
    Immunotherapies & Innovations for Infectious Diseases congress, 9-10th December, 2020.
  • A respiratory syncytial virus (RSV) F protein nanoparticle vaccine focuses antibody responses to a conserved neutralization domain.
    Swanson K. A et al. (cf Material & methods)
    Science Immunology, 2020 May 01; 5 (47).
    Sci Immunol
  • Development of a cynomolgus macaque model of infection with hRSV to evaluate therapeutic approaches.
    Blanc SC et al.
    Infectious Diseases Models for Innovative Therapies (IDMIT) Symposium 2016, 10 June 2016, Paris.
    IDMIT
  • Development of a cynomolgus macaque model of infection with hRSV to evaluate therapeutic approaches.
    Blanc SC et al.
    Therapeutic Monoclonal Antibodies for Respiratoy Diseases (TMARD): current challenges and perspectives, 31 March-1 April 2016, Tours.
    TMARD
  • Respiratory syncytial virus infection in macaques is not suppressed by intranasal sprays of pyrimidine biosynthesis inhibitors.
    Grandin C et al.
    Antiviral Res. 2016 Jan 19;125:58-62.
    ScienceDirect

On-demand preclinical models: contact us to discuss your needs

The selection of the appropriate animal model to evaluate the efficacy of your drug candidates is critical to your preclinical research success.

Cynbiose is committed to providing you with clinically relevant animal models, outstanding surgical and technical capabilities as well as high-quality data.

For more information, visit our specific page dedicated to customized efficacy models.

We’d be pleased to discuss your needs and projects. Feel free to contact our teams.

In vitro assays for aerosol therapies

Objectives

  • Assessment of aerosol therapies in the airways – nose-to-brain delivery
  • Assessment of aerosol therapies in the lungs

 

Please contact Cynbiose Respiratory for more information.

Pharmacokinetics including pulmonary PK

More information on the dedicated web page here.

For pulmonary pharmacokinetics, please contact Cynbiose Respiratory.

Nasal and pulmonary biodistribution

For more information, please refer to Cynbiose Respiratory‘s website.

Pharmacodynamics

More information here.

Early toxicology studies

Type of studies

  • Single and repeated doses, dose escalating studies
  • Immunosafety, immunogenicity
  • Pulmonary tox and respiratory function
  • Dose Range Finding (DRF)
  • Maximum Tolerated Dose (MTD)

Type of test item

  • Immunotherapies
  • Antibodies, ADC, …
  • Cell therapies, gene therapies, oncolytic virus
  • Oligonucleotides, antisense oligonucleotides
  • Therapeutic vaccines such as DNA vaccines, RNA vaccines
  • Recombinant proteins, recombinant enzymes
  • Peptides
  • Oncolytic viruses (BSL2 biocontainment, GMO C2)
  • Small molecules, ….

non-exhaustive list