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Pre-immunization of diet-induced obese male mice with inactivated pathogens increases power in a liraglutide
Caroline Falkenberg1, Dorte B Sørensen1, Camilla Hf Hansen1
1Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Pre-immunization with inactivated antigens has been developed as an alternative to the use of 'dirty' mice, which in contrast to specific pathogen free (SPF) mice, harbour a range of pathogens. Within certain research areas, such mice are considered better models for humans than SPF mice, as they have an immune system that better mirrors human immunity. We inactivated murine adenovirus type 1 (FL), minute virus of mice, mouse hepatitis virus (A59), respirovirus muris (Sendai), Theiler's encephalomyelitis virus (GD7) and Mycoplasma pulmonis by ultraviolet irradiation. We show that pre-immunization with these inactivated pathogens combined with adjuvant prior to the dietary induction of obesity in C57BL/6NTac mice substantially reduced the group sizes needed for showing an effect of the GLP-1 receptor analogue, liraglutide. Nesting, open field and novel object behaviours of the mice were unaffected. We conclude that pre-immunization with inactivated pathogens may be a simple tool to increase power in this type of intervention study on the DIO mouse model.
Pre-immunization with inactivated antigens has been developed as an alternative to the use of 'dirty' mice, which in contrast to specific pathogen free (SPF) mice, harbour a range of pathogens. Within certain research areas, such mice are considered better models for humans than SPF mice, as they have an immune system that better mirrors human immunity. We inactivated murine adenovirus type 1 (FL), minute virus of mice, mouse hepatitis virus (A59), respirovirus muris (Sendai), Theiler's encephalomyelitis virus (GD7) and Mycoplasma pulmonis by ultraviolet irradiation. We show that pre-immunization with these inactivated pathogens combined with adjuvant prior to the dietary induction of obesity in C57BL/6NTac mice substantially reduced the group sizes needed for showing an effect of the GLP-1 receptor analogue, liraglutide. Nesting, open field and novel object behaviours of the mice were unaffected. We conclude that pre-immunization with inactivated pathogens may be a simple tool to increase power in this type of intervention study on the DIO mouse model.
Frequently Asked Questions
Based on this study's findings, pre-immunizing C57BL/6NTac mice with UV-inactivated pathogens like Mouse Hepatitis Virus (A59) creates an antigen-experienced immune system. This immunological maturation reduces the group sizes required to detect the weight-loss effects of the GLP-1 receptor analogue, liraglutide, by increasing the study's statistical power.
The researchers used a cocktail containing Ultraviolet (UV) irradiated Murine Adenovirus Type 1 (FL), Minute Virus of Mice (MVM), Mouse Hepatitis Virus (A59), Respirovirus Muris (Sendai), Theiler's Encephalomyelitis Virus (GD7), and the bacterium Mycoplasma pulmonis to simulate natural microbial exposure.
The study utilized Ultraviolet (UV) irradiation to render pathogens like Respirovirus muris non-replicating while preserving their antigenic structures. This specific method enabled the researchers to safely prime the immune systems of SPF mice without the risk of active infection or spreading disease within the facility.
The authors assessed the safety of the protocol by monitoring nesting behavior, open field activity, and novel object recognition. Results showed that the immunization with inactivated pathogens did not alter these behavioral metrics, confirming the protocol's suitability for use in diet-induced obesity (DIO) intervention studies.
The study's authors propose that pre-immunization with inactivated pathogens is a simple, effective tool to increase statistical power in diet-induced obesity (DIO) models. They conclude this approach provides a more human-like immune profile, potentially improving the translational accuracy of GLP-1 receptor analogue intervention studies.
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