Model of viral respiratory tract infection in BALB/c mice


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).

Species

Mouse, other species on request

Field of application: substance testing, infectious diseases

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.

  • 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)
  • assessment of clinical symptoms after viral challenge (in vivo)
  • assessment of clinical symptoms after viral challenge (in 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
  • Quantitative RT-PCR
  • 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

  • Matthias Tenbusch, Thomas Grunwald, Thomas Niezold, Michael Storcksdieck genannt Bonsmann, Drew Hannaman, Stephen Norley, Klaus Überla. 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.

  • Victoria Stab, Sandra Nitsche, Thomas Niezold, Michael Storcksdieck Genannt Bonsmann, Andrea Wiechers, Bettina Tippler, Drew Hannaman, Christina Ehrhardt, Klaus Überla, Thomas Grunwald*, Matthias Tenbusch*. 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

  • Daowan Lai, Damian Odimegwu, Charles Esimone, Thomas Grunwald, Peter Proksch. Phenolic compounds with in vitro activity against respiratory syncytial virus from the Nigerian lichen Ramalina farinacea. Planta Med. 2013 Oct;79(15):1440-6.

  • Thomas Grunwald*, Matthias Tenbusch*, Reiner Schulte, Katharina Raue, Hans Wolf, Drew Hannaman, Rik de Swart, Klaus Überla, Christiane Stahl-Hennig. Novel vaccine regimen elicits strong airway immune responses and control of respiratory syncytial virus in nonhuman primates. J Virol. 2014 Apr 88.

*Contributed equally.