Fraunhofer Institute for Cell Therapy and Immunology IZI
Fraunhofer Institute for Cell Therapy and Immunology IZI

Model of viral respiratory tract infection in BALB/c mice

Species

Mouse, other species on request

Fields of application

Infections with viruses targeting the respiratory tract are widely analyzed in BALB/c mice. Therefore the animals were infected intranasally with viruses like the human Respiratory Syncytial Virus or different strains of Influenza viruses. After 2 days of viral challenge animals develop in dependence of the virus used different clinical symptoms.

Viral load and immunopathology is measured by state-of-the-art technologies.

The models can be used for the following fields of application:

  • Influence of immune response after viral infection
  • Vaccine development
  • Therapeutic / prophylactic efficacy of antiviral / immunmodulatory agents

Endpoints / outcome parameter

  • Viral load in lung tissue and BALF (ex vivo)
  • Assessment of clinical symptoms after viral challenge (in vivo)
  • Immune cells in blood and BALF (bronchoalveolar lavage fluid)
  • Binding and neutralizing antibody titer (ex vivo)
  • Airway remodelling (infiltration of different cell types ex vivo)
  • Cytokine levels in spleen and BALF (ex vivo)

Readout parameter

  • Quantitative RT-PCR
  • Flow cytometry
  • ELISA / CBA (cytometric bead array)
  • Histology / Cytology (various classical histological stains)
  • Immunohistochemistry
  • Imaging: BLI, CT, MRT

Quality management and validation

  • Controls
  • Blinded induction
  • Blinded data collection and analysis
  • Randomisation
  • Allocation concealment
  • Biometric Expertise
  • Internal quality management

References

Tenbusch M, Grunwald T, Niezold T, Storcksdieck Genannt Bonsmann M, Hannaman D, Norley S, Überla K. Codon-optimization of the hemagglutinin gene from the novel swine origin H1N1 influenza virus has differential effects on CD4(+) T-cell responses and immune effector mechanisms following DNA electroporation in mice. Vaccine. 2010 Apr 26.

Stab V, Nitsche S, Niezold T, Storcksdieck Genannt Bonsmann M, Wiechers A, Tippler B, Hannaman D, Ehrhardt C, Überla K, Grunwald T*, Tenbusch M*. Protective efficacy and immunogenicity of a combinatory DNA vaccine against Influenza A Virus and the Respiratory Syncytial Virus. PLoS One. 2013 Aug 14;8(8):e72217

Lai D, Odimegwu D, Esimone C, Grunwald T, Proksch P. Phenolic compounds with in vitro activity against respiratory syncytial virus from the Nigerian lichen Ramalina farinacea. Planta Med. 2013 Oct;79(15):1440-6.

Grunwald T*, Tenbusch M*, Schulte R, Raue K, Wolf H, Hannaman D, de Swart R, Überla K, Stahl-Hennig C. Novel vaccine regimen elicits strong airway immune responses and control of respiratory syncytial virus in nonhuman primates. J Virol. 2014 Apr 88.

*Contributed equally.

Viral load after vaccination and challenge. A: Immunization and viral challenge with the human Respiratory Syncytial Virus at the indicated time points. Here, at week 0 the animals were boosted with a genetic vaccine and challenged 10 weeks later. Additionally, the time points of bleeding and bronchoscopy to analyze systemic immune responses and viral load in bronchoalveolar fluid were shown. B: Viral load after challenge in the immunized group E in comparison to the untreated group G at the indicated days post challenge (dpc).
© Fraunhofer IZI
Viral load after vaccination and challenge. A: Immunization and viral challenge with the human Respiratory Syncytial Virus at the indicated time points. Here, at week 0 the animals were boosted with a genetic vaccine and challenged 10 weeks later. Additionally, the time points of bleeding and bronchoscopy to analyze systemic immune responses and viral load in bronchoalveolar fluid were shown. B: Viral load after challenge in the immunized group E in comparison to the untreated group G at the indicated days post challenge (dpc).