Testing Immunotherapies using the OVA Challenge Model
The immune systems of mice and humans are shockingly similar. Although it is true that experimental data from mice cannot be immediately translated and applied to humans, work with gnotobiotic mice is a viable and realistic method of understanding microbiota-mediated oral immune tolerance and studying potential immunotherapies. Given the daunting complexity of the human microbiome, its involvement in innate & adaptive immunity, and its ability to be influenced by a variety of genetic and environmental factors, gnotobiotic mice are an ideal model to understand and characterize immune-mediated and microbiota-related inflammatory diseases.
The interface between the immune system and the microbiome are areas of active research, specifically the microbiome’s role in immune response to nucleic acid vaccine administration. Studies have shown the microbiome to be a determinant in vaccine response, and characterizing this determinant allows for the maximization of vaccine efficacy via microbial adjuvants.¹ The microbiome plays a role in other aspects of immunity and oral tolerance as well, such as in the regulation of regulatory T-cells and immune-mediated inflammatory diseases.
Immune-mediated inflammatory diseases, such as autoimmune diseases and allergies - characterized by inflammation, lack of a normal immune response, and failure of immunological tolerance - are multifactorial and systemic. Designing immunotherapies to treat these diseases is, therefore, complex. OVA is used as a model antigen to study antigen-specific immune responses (i.e. in vaccine research) and to induce IgE-mediated food allergy models. For example, many labs use the OVA challenge model in mice: mice are sensitized and challenged with OVA to induce an antigen-specific immune response and mimic an inflammatory disease state. This allows researchers to better understand the mechanisms underlying the overreactive immune response and test its modulation via microbiota or microbial-derived adjuvants. For example, the OVA challenge model was used to induce asthma in mice in order to test Amomum compactum as an adjuvant treatment.² In this experiment, it was able to suppress Th2 cytokines, decrease eosinophils, and decrease IgE release in OVA-sensitized/challenged mice.²
Oral tolerance can be influenced by the intestinal consortia of microbiota. In addition, probiotic therapies and microbial adjuncts have been shown to promote Tregs and modulate Th1 vs Th2 immune responses.³ Although the current medical field is far from an efficacious, clinically-tested probiotic that can modulate the microbiome to systemically treat immune-mediated inflammatory diseases, it is feasible to define the mechanisms and microbial metabolites that induce microbiota-mediated immune tolerance by using OVA-challenged mice models. Toll-like receptors are another therapeutic target area, as they initiate immune-mediated inflammation after recognizing PAMPs and may play a role in autoimmunity. This research can then be applied towards adjuvant immunotherapies for the systemic treatment of autoimmune disorders and allergies.
References
Johnson AMF, Hager K, Alameh M-G, Van P, Potchen N, Mayer-Blackwell K, et al. The regulation of nucleic acid vaccine responses by the microbiome. J Immunol [Internet]. 2023 [cited 2024 Feb 13];211(11):1680–92. Available from: https://journals.aai.org/jimmunol/article/211/11/1680/266096/The-Regulation-of-Nucleic-Acid-Vaccine-Responses
Lee J-A, Lee M-Y, Seo C-S, Jung DY, Lee N-H, Kim J-H, et al. Anti-asthmatic effects of an Amomum compactum extract on an ovalbumin (OVA)-induced Murine asthma model. Biosci Biotechnol Biochem [Internet]. 2010;74(9):1814–8. Available from: https://www.jstage.jst.go.jp/article/bbb/advpub/0/advpub_100177/_pdf
Ho H-E, Bunyavanich S. Microbial adjuncts for food allergen immunotherapy. Curr Allergy Asthma Rep [Internet]. 2019;19(5). Available from: http://dx.doi.org/10.1007/s11882-019-0859-1