RSV2018-10-26T03:51:18+00:00

RSV Disease Models

Aragen Bioscience has conducted over 100 RSV studies in rodent models,  gaining the experience needed to handle even the most complex projects. With state-of-the-art facilities, a choice of rodent models, and a broad-range of readouts, we’re ready for your pre-clinical efficacy testing project.

Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV) causes a broad range of respiratory disease, especially in infants and the elderly.Mouse Model

Recent epidemiological data indicates that over 3 million children under the age of 5 are hospitalized due to RSV-related infections, with over 200,000 deaths annually. There is also a growing body of evidence suggesting that hRSV is responsible for significant morbidity among the elderly and in adults with underlying chronic illness1. Limited treatment options are driving therapeutic research programs worldwide, including 51 RSV vaccine candidates currently under development2.

Laboratory animal studies permit detailed experimental modeling of hRSV disease, with each model and experimental design offering unique advantages. Aragen has completed over 100 RSV-related studies and leverages that experience with every new project. That’s why we precisely tailor each project to your needs by offering a choice of rodent models (BALB/c and Cotton Rat) as well as a broad range of model readouts.

A Choice of Rodent Models

Cotton Rat

The cotton rat (Sigmodon hispidus) has become a standard model for evaluation of vaccines, antivirals, and neutralizing antibodies (e.g., palivizumab)3 and has facilitated preclinical testing for anti-hRSV therapeutic modalities. Cotton rats are more permissive for hRSV replication than standard mouse models. The model has shown to be highly predictive. Synagis® advanced to clinical trials based on cotton rat efficacy and safety studies, obviating the need for testing in primates. However the cotton rat model has several limitations. Compared to mice there are fewer available immunological4. Inbred strains of cotton rats are commercially available, but no transgenic or gene-deleted strains have been constructed. Cotton rats are far more difficult to handle than standard mouse strains and have special husbandry requirements.

BALB/c Mouse

BALB/c has been popular for experimental modeling of human hRSV disease for decades. The mouse model is semi-permissive for RSV A strains, however it is not useful for RSV B strains. Combined with a broad range of available mouse-specific reagents and molecular tools, mice can be used to explore specific pathophysiologies and disease patterns. Their small size minimizes the amount of required test compound. At Aragen, they have proven to be ideal for proof-of-concept studies.

BALB/c Mouse Cotton Rat
  • Semi-permissive for RSV A strains (not useful for RSV B)
  • Appropriate for proof-of-concept studies
  • More reagents for immune readouts
  • Non-USDA covered species
  • Small amount of test compounds required
  • Useful for both RSV A and RSV B strains
  • Clinically relevant model used for Synagis® approval
  • Model for FI-RSV induced enhanced disease
  • USDA regulated

RSV Strains Available

Aragen uses a panel of well characterized, high-titer stocks of common laboratory viral strains.

  • RSV-A2, RSV-Long, RSV-B-18537
  • RSVA2-line19F, licensed from Emory University

A Broad Range of Readouts

Aragen can provide a variety of readouts from standard plaque assays to custom assays for all your analytic needs.

  • RSV titers from lungs, nasal turbinate and bronchavoloar lavage fluids
  • Lung weights and other organ weights, snap frozen or fixed for histology
  • qPCR analysis of RSV viral transcripts in lungs or other organs
  • Virus neutralization assays
  • ELISA serum analysis
  • Cytokine analysis on BAL or lung homogenates
  • ELISpot assays for B and T cell analysis
  • BAL fluid collection with total leukocyte counts and differentials
  • Serum or plasma
  • Serum chemistry and whole blood differentials

Readout Example: Replication in Lungs and Nasal Tissue in Dose Titration Experiments

RSV readout examples

Female BALB/c 6-8 weeks old, transient weight loss at the higher dose, harvest day 5

Aragen offers a state-of-the-art facility with a dedicated a BSL2 suite, a tissue-culture lab and all the instrumentation required for a broad range of analytical methods. All studies are reviewed by Aragen’s Institutional Animal Care and Use Committee (IACUC). Our PhD level scientists have greater than ten years of experience in industry and academia.

Ready to learn more? Contact us and discover how we can move your RSV projects forward.

Aragen Posters

In Vivo Models and In Vitro Assays for Human RSV Infection – Pre-Clinical Antibody, Small Molecule and Vaccine Development

 

References

1) Bem RA, Domachowske JB, Rosenberg HF. Animal models of human respiratory syncytial virus disease. American Journal of Physiology – Lung Cellular and Molecular Physiology. ;301(2):L148-L156. doi:10.1152/ajplung.00065.2011., 2011

2) World Health Organization, 2017.

3) Prince GA, Hemming VG, Horswood RL, Baron PA, Chanock RM. Effectiveness of topically administered neutralizing antibodies in experimental immunotherapy of respiratory syncytial virus infection in cotton rats. Journal of Virology 61(6): 1851–1854, 1987.

4) Niewiesk S, Prince G. Diversifying animal models: the use of hispid cotton rats (Sigmodon hispidus) in infectious diseases. Lab Anim 36: 357–372, 2002.

5) Moore ML1, Chi MH, Luongo C, Lukacs NW, Polosukhin VV, Huckabee MM, Newcomb DC, Buchholz UJ, Crowe JE Jr, Goleniewska K, Williams JV, Collins PL, Peebles RS Jr. A chimeric A2 strain of respiratory syncytial virus (RSV) with the fusion protein of RSV strain line 19 exhibits enhanced viral load, mucus, and airway dysfunction. Journal of Virology 83 (9):4185-94, 2009.