Infectious Diseases

Aragen Bioscience Infectious Disease Models

Appropriate in vivo rodent models are critical to evaluate the safety and efficacy of antibodies, small molecules, and vaccines for the treatment of infectious diseases. Aragen Bioscience’s expertise in a number of infectious disease models, along with its diverse portfolio of ex-vivo analyses makes us an ideal partner for discovery and pre-clinical evaluation of your candidates.

• State of the art BSL-2 vivarium and laboratories
• In-vivo and Ex-vivo readouts
• Viral Titrations
• Immune response readouts such as neutralization assays, ELISA, ELISpots, FACS.
• Whole Body Plethysmography, flexiVent, and Pulse Oximetry are available for respiratory disease pathogens.
• Histology

Aragen Bioscience infectious disease models

• Respiratory syncytial virus (RSV) in mice and cotton rats
• Mouse cytomegalovirus (mCMV)
• Clostridium difficile-associated diarrhea model in hamsters and mice
• Influenza and Human Metapneumovirus mouse models
• Immunogenicity studies to evaluate vaccine candidates.
• Mouse coronavirus MV-A59
• Citrobacter-induced colitis in mice

Respiratory syncytial virus (RSV) in mice and cotton rats

Respiratory syncytial virus (RSV) is a common viral pathogen that primarily affects the respiratory tract, particularly in infants, young children, and the elderly. RSV is a member of the Paramyxoviridae family and is a significant cause of respiratory tract infections, including bronchiolitis and pneumonia. RSV vaccines can potentially reduce the morbidity and mortality associated with RSV infections, especially in high-risk populations. Vaccination can also help reduce healthcare costs associated with RSV-related hospitalizations and treatment. Antivirals could provide effective treatment options for RSV infections, reducing the severity and duration of illness. Aragen Bioscience offers RSV preclinical efficacy and safety studies using appropriate in vivo rodent models to enable development of anti-RSV antibodies, small molecules, and vaccines.

Experimental RSV Vaccine model

Key Readouts:

• Lung and nose viral titers by plaque assay
• Lung and nose viral genome copy numbers by qPCR.
• Immune modulation: Neutralization Assays, ELISA, ELISpot, FACS, MSD
• Bronchoalveolar lavage with cytokine and infiltrating cell analyses
• Histology
• Lung function readouts: Whole Body Plethysmography and flexiVent.

Experimental RSV Model for evaluation of anti-RSV antibodies, small molecules

Key Readouts:

• Lung and nose viral titers by plaque assay
• Lung and nose viral genome copy numbers by qPCR.
• Modulation of Immune responses: FACS, MSD
• PK bleed during in-life
• ELISA serum analysis-blood chemistries

Mouse Cytomegalovirus: Antiviral Pre-clinical Model

Human CMV, like other herpes viruses, establish life-long persistent and latent infections in their host (like cold sores, chicken pox/shingles). Most people become infected with human CMV during early childhood and adolescence with few to no symptoms in the immunocompetent. Human CMV infection (primary or reactivation) can cause serious disease and mortality in immunocompromised individuals (organ transplants and AIDS patients).

Human CMV infections in utero are problematic.

• Congenital CMV infections occur at a frequency of 1-2% of all live births.
• A sizable portion of those infections result in central nervous system birth defects such as hearing loss and learning disabilities (Handbook of Animal Models of infection, 1999; chapter 111)
• Typical scenario: First child brings home CMV from daycare and infects CMV seronegative pregnant mother.

Current Modalities

Drugs such as Ganciclovir, valganciclovir, foscarnet, maribavir and cidofovir are prescribed and have dramatically improved outcomes for immunocompromised hosts. However, clinical utility of most of these drugs is limited by poor oral bioavailability, associated toxicities, and the potential for development of resistance with prolonged use. There is a critical need for novel therapeutic agents to address limitations of FDA approved drugs.

Benefits of the mouse CMV BALB/c model

There is a strict species specificity amongst the CMV viruses, making it difficult to evaluate hCMV viral infections in rodent models. Because mCMV and hCMV share similarity at the genetic and nucleotide level and infection of mice with mCMV sets up an infection with many similarities to human disease, the mCMV model has proven to be an excellent model for predicting anti-viral drug efficacy in human CMV disease (Handbook of Animal Models of infection, 1999; chapter 111). It is not as useful for vaccine candidates and biologics.

Aragen Bioscience offers mCMV preclinical efficacy and safety studies using an appropriate in vivo rodent model to enable development of anti-CMV antiviral drugs.

Experimental mCMV Model for evaluation of anti-CMV vaccines

• Day 0: Infect 8-9wk BALB/c mice with desired dose (lethal or non-lethal) of 3X-salivary gland passaged mCMV.
• Monitor weight and survival throughout the study
• Ganciclovir used as positive control/standard of care.
• Day of harvest: Collect salivary glands spleen, liver heart, lungs kidney for titration.

Key Readouts

• Body Weight
• Survival
• Viral titration by plaque assay or qPCR

Influenza and Human Metapneumovirus mouse models

Immunogenicity studies to evaluate vaccine candidates.

Mouse coronavirus MV-A59

Citrobacter-induced colitis in mice