The OVA-induced Asthma Model in Mice and Rats: An Overview

July 06, 2023 /

Asthma is a chronic respiratory disease that is estimated to affect 262 million people worldwide and kill approximately 455,000 annually. It is characterized by airway inflammation, bronchoconstriction and airway hyperresponsiveness. These features can significantly impact the quality of life of affected individuals, and although symptom management is feasible, there is no known cure for this condition. The complexity of asthma and the factors contributing to its onset make its treatment and management challenging even for the most experienced healthcare professionals and pharmacologists. One commonly used animal model of asthma is the ovalbumin-induced asthma model. This model involves sensitizing animals to ovalbumin, which is a common allergen, using an adjuvant such as aluminum hydroxide. The sensitization process primes the immune system to recognize ovalbumin as a foreign substance and mount an immune response against it. After sensitization, the animals are challenged with aerosolized albumin, which is delivered directly into the lungs via a nebulizer or inhalation chamber. The challenge with ovalbumin leads to an inflammatory response in the lungs, which includes airway hyperresponsiveness, mucus production, and eosinophil infiltration. In the OVA induced asthma model, this can be measured by assessing changes in lung function, such as airway resistance or lung compliance. Mucus production refers to the increased secretion of mucus in the airways, which can obstruct airflow. In the OVA-induced asthma models, this can be assessed by staining lung tissue with a dye that highlights mucus producing cells. Eosinophilic infiltration is a characteristic feature of inflammatory airway reaction occurring because of asthma. In addition to eosinophils, other immune cells, such as neutrophils, lymphocytes, and macrophages, can also be involved in the inflammatory process of asthma. The levels of these cells in the bronchoalveolar lavage fluid (BALF) can provide insights into the specific inflammatory status and immune responses associated with different asthma phenotypes or exacerbations.

With an estimated total annual cost of $81.9 billion in the United States only (factoring in medical care, absenteeism, and mortality), the burden of asthma on the healthcare system needs to be dealt with swiftly.

Although the exact cause of asthma remains unknown, OVA-induced asthma models have been instrumental in uncovering the underlying mechanisms of the disease.

 

Overview of the OVA-Induced Asthma Model:

Recent studies have continued to use OVA-induced asthma models to investigate the pathophysiology of asthma and potential therapeutic interventions. For instance, a 2021 study by Chelladurai et al. demonstrated that blocking the interaction between OX40L and its receptor OX40 using an antibody reduced airway hyperresponsiveness and inflammation in an OVA-induced asthma model in mice (Chelladurai et al., 2021). Another study by Liu et al. (2020) used an OVA-induced asthma model to investigate the potential therapeutic effects of a novel molecule, FXYD6, which is involved in regulating ion transport in airway epithelial cells. The study found that FXYD6 overexpression attenuated airway inflammation, hyperresponsiveness, and remodeling in the OVA-induced asthma model in mice (Liu et al., 2020).

H&E Stain of a Lung Section

 

Role of IgE in the Model:

In the OVA-induced asthma model, IgE can play a significant role in allergic reactions by sensitizing mast cells and basophils to ovalbumin (OVA). However, it is important tot note that in order to effectively replicate the model, multiple mucosal OVA challenges are required to drive the IgE-mediated response. Upon re-exposure to OVA, the allergen binds to the IgE antibodies on sensitized mast cells and basophils, leading to the release of various inflammatory mediators that contribute to the development of asthma symptoms. These mediators, such as histamine, leukotrienes, and cytokines, can induce airway hyperresponsiveness, mucus production, and airway inflammation, which are considered important aspects of asthma pathogenesis.

 

Airway Hyperresponsiveness in the OVA-induced Asthma Model:

Several mechanisms have been implicated in the development of AHR in the OVA model. OVA-induced inflammation in the airways can lead to increased airway smooth muscle contraction, which contributes to airway narrowing. This inflammation can be driven by various immune cells such as Th2 cells, eosinophils, mast cells, and basophils. The activation of these immune cells leads to the release of cytokines and chemokines that recruit more immune cells, promote inflammation, and contribute to AHR. In addition, the recruitment of inflammatory cells, such as eosinophils and mast cells, can release various mediators that can further promote airway hyperresponsiveness, such as histamine, leukotrienes, and prostaglandins. These mediators can increase bronchial smooth muscle tone, enhance microvascular permeability, and promote mucus secretion, all of which contribute to AHR.

 

History of the OVA-Induced Asthma Model:

The ovalbumin-induced asthma model was first described in the 1970s and has since become one of the most widely used models for studying asthma (1). The model was initially used to investigate the role of immunoglobulin E (IgE) in the development of asthma. Since then, the model has been used to study various aspects of the disease, including the role of cytokines, chemokines, and other immune system molecules in the pathogenesis of asthma.

 

Comparison of OVA-Induced Asthma vs. Other Asthma Models:

Several animal models have been developed to study asthma, such as the house dust mite model, the cockroach antigen model, and others. While each model has its advantages and limitations, the ovalbumin-induced asthma model is still considered one of the most reliable and widely used models for studying asthma (2). The model is cost-effective and there are genetically engineered transgenic mice available for investigating OVA-specific responses, which is essential for studying the mechanisms of the disease, and for evaluating new biologics. However, it is important to note that no single animal model can fully replicate the complexity and heterogeneity of human asthma.

 

Best Practices When Using the Model:

Using high-quality ovalbumin to minimize batch-to-batch variability, standardizing the animal vendors, and the route and dose of ovalbumin exposure to ensure consistency. Additionally, using a suitable control group to account for any nonspecific effects of ovalbumin and monitoring the animals for signs of distress or illness while ensuring appropriate care are crucial aspects of conducting the study.

 

FAQ:

Q: How does the ovalbumin-induced asthma model compare to human asthma?

A: While animal models cannot fully replicate human disease, the ovalbumin-induced asthma model can provide valuable insights into the underlying mechanisms of asthma. However, caution should be exercised when extrapolating findings from animal models to human disease. For example, there may be differences in the immune response between mice and humans, and ovalbumin may not be a relevant allergen for all patients with asthma.  The OVA model is best used to model patients with a TH2 asthma phenotype.

 

Q: What are the advantages of the ovalbumin-induced asthma model compared to other animal models?

A: The ovalbumin-induced asthma model is one of the most widely used and reliable models for studying asthma. One of the main advantages of this model is the ability to mimics key inflammatory features of asthma, including airway hyperresponsiveness, mucus production, eosinophilic infiltration, and cytokine release. These features closely resemble the characteristics seen in human asthma, making the model relevant for studying underlying mechanisms and evaluating anti-inflammatory interventions.

 

Q: What are the limitations of the ovalbumin-induced asthma model?

A: Like all animal models, the ovalbumin-induced asthma model has its limitations. One limitation is that the immune response in mice may not accurately reflect the immune response in humans. For example, the relative dominance of Th2 immune responses in the ovalbumin model may not fully reflect the immune profiles seen in all types of human asthma, which can involve various immune cell types and cytokines. Additionally, the ovalbumin-induced asthma model is an acute model of asthma that does not fully capture the chronic and progressive nature of the disease. Furthermore, ovalbumin is not a common human allergen, and the model does not account for the contribution of non-allergic triggers to the development of the disease.  The HDM model is more mixed TH1/2/17 phenotype model is also offered by PL,

 

Q: Can ovalbumin-induced asthma models be used to study the effects of therapeutic interventions?

A: Yes, ovalbumin-induced asthma models have been used to study the effects of various therapeutic interventions, including anti-inflammatory agents and bronchodilators. By using these models, researchers can test the efficacy and safety of potential asthma treatments before moving to human clinical trials.

 

Q: What are some best practices for using ovalbumin-induced asthma models?

A: To ensure reliable and reproducible results, it is essential to follow best practices when using ovalbumin-induced asthma models. These practices include using high-quality ovalbumin to minimize batch-to-batch variability, standardizing the animal vendors, and the route and dose of ovalbumin exposure to ensure consistency. Additionally, using a suitable control group to account for any nonspecific effects of ovalbumin and monitoring the animals for signs of distress or illness while ensuring appropriate care are crucial aspects of conducting the study. Furthermore, researchers should consider using multiple models of asthma to validate their findings and to account for the limitations of each model, such as the HDM Asthma Model.

 

Q: Are OVA-induced asthma models only in rodents? What would an analogous asthma model be in non-human primates?

A: Ovalbumin (OVA)-induced asthma models have been primarily used in rodents, such as mice and rats, to study the pathophysiology of asthma and to evaluate potential therapeutic interventions. However, there have been some studies that have also used OVA-induced asthma models in other species, such as guinea pigs and rabbits.

 

Sourcing Your Asthma Study:

Our OVA-induced asthma model faithfully reproduces pulmonary inflammation (eosinophil infiltration), airway hyperresponsiveness, and the elevated IgE levels found in asthma. Coupled with our many years of experience in pharmacology, PharmaLegacy has the expertise and resources to provide comprehensive and reliable preclinical services for respiratory drug development. Choose right when looking for a CRO. Choose PharmaLegacy.

 

References:

  1. Alcorn, J. F., Crowe, C. R., Kolls, J. K. (2011). TH17 cells in asthma and COPD. Annual Review of Physiology, 73, 495-516.
  2. Carroll, O. R., Pillar, A. L., Brown, A. C., Feng, M., Chen, H., & Donovan, C. (2023). Advances in respiratory physiology in mouse models of experimental asthma. Frontiers in Physiology, 14. https://doi.org/10.3389/fphys.2023.1099719
  3. Chelladurai, P., Sehgal, I. S., Dhooria, S., Agarwal, R. (2021). Targeting the OX40-OX40L pathway in allergic asthma: a preclinical study. Immunotherapy, 13(1), 15-27.
  4. Das, S., Miller, M., Broide, D. H. (2019). Chromogranin A: a novel mediator of asthma pathogenesis and therapeutic target. Journal of Allergy and Clinical Immunology, 143(4), 1372-1379.
  5. Fallon, P. G. (2019). The high and lows of type 2 asthma and mouse models. Journal of Allergy and Clinical Immunology, 105(2). https://doi.org/10.1016/s0091-6749(00)70138-2
  6. Fujisawa, T., Joshi, B. H., Puri, R. K. (2019). IL-13 regulates cancer invasion and metastasis through IL-13Rα2 via ERK/AP-1 pathway in mouse model of human ovarian cancer. Molecular Cancer Therapeutics, 18(5), 903-914.
  7. Liu, Z., Wang, Q., Wang, J., Yao, X., Huang, J., Yang, Z., … & Lu, X. (2020). Overexpression of FXYD6 attenuates airway inflammation, hyperresponsiveness and remodeling in a murine model of OVA-induced asthma. Molecular Immunology, 117, 1-10.
  8. Reber, L. L., Marichal, T., Galli, S. J. (2019). New models for analyzing mast cell functions in vivo. Trends in Immunology, 40(4), 361-373.
  9. Sathish, V., Thompson, M. A., Bailey, J. P., Pabelick, C. M., Prakash, Y. S., Sieck, G. C. (2020). Electrostatic atomization-based pulmonary administration of ovalbumin in mice: development of a novel in vivo asthma model. Journal of Aerosol Medicine and Pulmonary Drug Delivery, 33(2), 98-110.
  10. Yan, X., Zhang, Y., Wang, L., Chen, H., Wang, J., Gao, J., & Zou, X. (2020). Plumbagin alleviates airway inflammation in ovalbumin-induced asthma mice through suppressing the activation of nuclear factor kappa B and mitogen-activated protein kinases. Journal of Immunology Research, 2020, 1-13.
  11. Zhang, Y., Tang, H., Cai, L., Zhao, J., Liu, X., Yao, D., … & Zhang, H. (2021). Nanoparticle-based targeted delivery of ovalbumin to dendritic cells for enhanced cellular immune response and asthma therapy. Journal of Materials Chemistry B, 9(19), 4072-4081.