Murine and Ferret Influenza Models

The pandemic of Swine flu which arose from Mexico and the constant threat of new strains such as H5N1, has highlighted the potential risk to human health that influenza poses globally, and the importance of developing novel anti-influenza drugs and improved vaccines. Charles River provides a range infection models including influenza models:

  • Mouse influenza model: The mouse model uses murine adapted virus strains, and due to the highly characterized nature of the murine immune system is particularly suited for lead identification and for analysis of multiple immunological parameters in vaccine design.
  • Ferret influenza model: Ferrets are uniquely sensitive to human influenza strains and display all of the key symptoms of infection, allowing the effects of novel drugs and vaccines to be tested on a wide range of human influenza viruses in a setting where the effects on classical influenza symptoms can be monitored.

Study Endpoints

  • Clinical Scores
  • Change in bodyweight and temperature
  • Survival
  • Antiviral in vitro readouts
    • Viral load – influenza virus titres in lung homogenates, nasal washes or BAL.
    • Cellular infiltrate and cytokines in BAL or lung homogenate
    • Gross pathology scores

 

Validation Data

Clinical scores in mice following intranasal infection with A/Puerto Rico/8/34 (H1N1)
Figure 1. Clinical scores following infection with PR8 (H1N1 influenza). Data are presented as mean clinical scores ± SEM (n=10).

 

Viral load in lung of mice infected with A/Puerto Rico/8/34 (H1N1)
Figure 2. Lung viral titres following infection with PR8 (H1N1 influenza). Data are presented as mean TCID50 ± SEM (n=2).

 

Influenza Model Frequently Asked Questions (FAQs)

  • Which animal models of influenza are most clinically relevant?

    The influenza models that are most frequently used are the mouse adapted H1N1 viral model or the ferret model. Mice are not naturally susceptible to human strains of influenza, the virus therefore needs to be passaged several times in order to cause infection. Ferrets however are susceptible to a wide range of human influenza strains and demonstrate similar symptoms to the human disease e.g. sneezing and lethargy, so can provide a model that is translatable into the clinic. Charles River offer both of these influenza models and can advise on the best option for your discovery program.

  • Why should I use the ferret influenza model?

    Ferrets are the only influenza model that is well suited to study both pathogenicity and transmissibility of human and avian influenza strains. They exhibit clinical symptoms associated with human influenza, including fever, nasal discharge, sneezing and lethargy. In addition both human and avian influenza strains replicate efficiently in their respiratory tracts, mirroring the transmissibility seen in humans.

  • What are the advantages our mouse models of influenza?

    Mice are widely used to model influenza, due their small size, reduced cost, the availability of species-specific reagents, and their highly characterized immune system. All of which makes them well suited for lead identification and to analyse the impact of the immune system on vaccine design. Although mice can’t be infected with most human strains of influenza, there are mouse adapted strains of H1N1, as well as reassortant viruses which have specificity for H3N2, H5N1 etc. which allows Charles River to test efficacy of clients influenza antivirals and vaccines.

  • How is efficacy of antivirals shown in influenza models?

    The main readout in mouse models of influenza is body weight loss. In ferret models of influenza other clinical signs are also exhibited e.g. sneezing and lethargy. In addition Charles River can use in vitro assays to assess viral load, in-life, in the lungs.