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
  • Screening of drug candidates (partnered) : in vitro cell lines (human bronchial epithelial cell lines, Vero 6) and ex vivo model (Human airway epithelial cell model)
  • Development of on-demand in vivo infectious models
  • Delivery routes: 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, antivirals, antibiotics…
Immunogenicity studies for vaccines Dedicated solution for inhaled products & aerosoltherapies
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Efficacy studies
  • SARS-CoV-2 / COVID-19 model
  • Tropical diseases: Dengue, …
  • Respiratory viral infections: hMPV, hRSV, measles, SARS-CoV-2
  • On-demand preclinical models: contact us to discuss your needs
Exploratory studies
  • Pharmacokinetics
  • Pharmacodynamics
  • Immunogenicity assessment
  • Infectious tropism- Viral tropism

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.

Tropical diseases: Dengue, …

Species

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

Pathogens

  • Dengue
  • On-demand pathogens

Infection method: Natural infection, SC, IV

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
  • 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
  • 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: 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.

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 assessment

Objectives

  • Assessment of the immune response in healthy nonhuman primates
  • Evaluation of route of administrations (PO, SC, IM, Intranasal, Nebulization, …)

Test items

  • Vaccines
  • Biologics

Readouts

  • Assessment of antibody responses : anti-drug antibody (ADA) and neutralizing antibody (nAb) assays
  • Seroneutralization assays depending on the pathogen
  • Assessment of humoral and cellular immune response

Infectious tropism- Viral tropism

Species

  • Cynomolgus macaque (Macaca fascicularis)

Objectives

  • Assessment of organ/tissue tropism

Readouts

  • Organs and tissues collection
  • Detection and quantification of viral DNA and RNA
  • Cellular tropism (FACs analysis)