Infectious diseases

Infectious diseases are caused by pathogenic microorganisms such as viruses, bacteria, parasites, … These diseases can cause high mortality as well as severe complications leading to heavy burdens of disability. They can also spread rapidly and lead to serious global health repercussions. Infectious diseases is the 3rd therapeutic area targeted by drugs undergoing preclinical development.

The NHP can be infected by many human pathogens, either in the wild or experimentally. As such, the non-human primate has been used to faithfully model various viral, bacterial or even fungal infections in various fields of interest for public safety. Among them, one can list viral or bacterial respiratory infections (hRSV, hMPV, measles, S. pneumoniae, coronaviruses such as SARS-CoV-2 / COVID – 19, tuberculosis, etc…), tropical diseases (Malaria, Zika, Leishmaniasis, Yellow fever…) or other chronic and life-threatening infections (SIV/HIV, hepatitis C…).

With its BSL 2/3 facility and long experience in non-human primate infectious models, Cynbiose can implement unique infectious models in an industrial setting, using either wild-type or GMO pathogens. These models can then be used as proof of concepts for the efficacy of novel vaccines, anti-viral, or anti-bacterial drugs.

 

PRECLINICAL EXPERTISE AND CAPABILITIES

  • Scientific advice on relevant species
  • Network of partners for strain sourcing
  • Route of administrations: IN, IT, IP, aerosolization, nebulization & classical ROA (SC, IM, ID, IV, …)
  • Sampling: nasal, laryngeal & nasopharyngeal swabs, BAL, blood, CSF, urine, feces, ultrasound-guided biopsies, …
  • Clinical monitoring: custom behavioral grid, implanted temperature loggers…
  • Thanks to state-of-the-art biological analyzers, we are able to conduct our clinical pathology analyses (biochemistry and complete blood count with differential) in a BSL1/2/3 setting, depending on the needs of the protocol
  • Histopathology of disease progression
  • Assays to measure serological, cell-mediated immune responses, bacterial or virus load: validated assays and custom-made assays on demand
  • Type of therapeutics (nebulized or not): vaccines, immunotherapies, antibodies, antiviral, antibiotics…

 

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Efficacy studies
  • Tropical diseases: Dengue, Malaria, Zika, Leishmaniasis…
  • Respiratory viral infections: SARS-CoV-2, hMPV, hRSV, measles
  • Respiratory bacterial infections
  • On-demand preclinical models: contact us to discuss your needs
Exploratory studies
  • Pharmacokinetics
  • Pharmacodynamics
  • Immunogenicity (vaccines)
  • Infectious tropism

Tropical diseases: Dengue, Malaria, Zika, Leishmaniasis…

Species

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

 

 

Pathogens

  • Dengue
  • Malaria
  • Zika
  • Leishmaniasis
  • Viral hepatitis C


Infection method:
Live mosquitoes, natural infection, SC, IV

Objectives

  • Infection tropism
  • Vaccines efficacy assessment
  • Route of infection

Readouts

  • Clinical follow-up
  • Body temperature
  • Clinical pathology : biochemistry and complete blood count with differential) in a BSL1/2/3 setting thanks to state-of-the-art biological analyzers
  • Ultrasound-guided needle biopsies
  • Histopathology
  • Custom readouts

Scientific publications

  • Preclinical development of immunotherapies for infectious diseases: relevance of the Non-Human Primate. Verset M, Contamin H. Immunotherapies for Infectious Diseases Congress (I4ID) 2017, 11-12 Déc. 2017, Lyon.
  • Plasmodium falciparum infected squirrel monkeys (Saimiri sciureus): a non-human primate model for the assessment of antimalarial efficiency of drug candidates. Grandin C. 12th European Primate Veterinarian (EPV) annual symposium, 27-28 Sept 2012, Lyon.
  • Measles vaccine expressing the secreted form of West Nile virus envelope glycoprotein induces protective immunity in squirrel monkeys, a new model of West Nile virus infection. Brandler S, Marianneau P, Loth P, Lacôte S, Combredet C, Frenkiel MP, Desprès P, Contamin H, Tangy F. J Infect Dis. 2012 Jul 15;206(2):212-9.
  • Experimental infection of squirrel monkeys with nipah virus. Marianneau P, Guillaume V, Wong T, Badmanathan M, Looi RY, Murri S, Loth P, Tordo N, Wild F, Horvat B, Contamin H. Emerg Infect Dis. 2010 Mar;16(3):507-10.
  • Early and strong immune responses are associated with control of viral replication and recovery in lassa virus-infected cynomolgus monkeys.
    Baize S, Marianneau P, Loth P, Reynard S, Journeaux A, Chevallier M, Tordo N, Deubel V, Contamin H. J Virol. 2009 Jun;83(11):5890-903.

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

Species

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

 

 

Pathogens

  • Human Respiratory Syncytial Virus (hRSV)
  • Human Metapneumovirus (hMPV)
  • SARS-CoV-2 / COVID-19
  • Measles

Infection method : Intratracheal microspray, intranasal

Readouts

  • Implanted body temperature measurement
  • Bronchoalveolar lavage
  • Nasal & nasopharyngeal swabs
  • Clinical pathology : biochemistry and complete blood count with differential) in a BSL1/2/3 setting thanks to state-of-the-art biological analyzers
  • Immunoassays
  • Transcriptomics
  • Custom readouts

Scientific publications

  • 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

 

Respiratory bacterial infections

A non-human primate infection model using S. Pneumoniae.

 

For more information, please contact Cynbiose Respiratory.

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.

Pharmacokinetics

Pharmacokinetics

  • Circulating drug kinetics following most routes of administration (more information)
  • Cutting-edge expertise for in vivo central pharmacokinetics 
    • Blood sampling
    • Cerebrospinal fluid (CSF) drug levels
    • Brain microdialysis to monitor neurotransmitters, drugs or metabolites in the extracellular cerebral fluid.
      Discover our proprietary platform Kine C3

Clinical follow-up and Bioanalysis

  • Daily clinical monitoring for the early detection of adverse effects
  • Monitoring of physiological parameters and other biomarkers of interest
  • Bioanalysis (more information)

Pharmacodynamics

More information here.

Immunogenicity (vaccines)

Objectives

  • Assesment of the immune response for vaccines in non-human primate preclinical models

Bioanalysis

  • Measurement of Anti-drug antibody (ADA)

 

Infectious tropism