New insights from AITox 2020!
The AITox seminars this year were quite interesting and informative, the organizers did a great job pivoting into the virtual world! If you missed the opportunity to attend, here are some highlights and what we learned.
Models of COVID-19
Dr. Jake McDonald from Lovelace Biomedical started the series of sessions with a presentation on the models of COVID-19. In his presentation, he noted the hACE2 mouse showed pronounced clinical manifestations, making this an ideal model for COVID research.
Hamster animal models are also becoming an integral tool in the fight against COVID-19. Hamsters are an effective tool in early efficacy studies, even though these models show milder symptoms in comparison to the mouse model. The third model reviewed in Dr. McDonald’s presentation included the African green monkey model, which showed very mild symptoms if any.
The researchers at Lovelace use a five-day hamster model as a screening tool. When it came to observing these models, the researchers found that monitoring temperature was not an ideal outcome because of its variability. Looking at the bodyweight and clinical observations was also arduous since differences between diseased and normal subjects were hard to identify by sight.
There aren’t many differences between the hamster and mouse models in terms of viral distribution in the lungs, nares, trachea, and brain. However, inhalation delivery with hamsters is not as easy because of their morphology..
Non-Human Primate (NHP) Models
In the United States, access to NHP models is limited to those working with Operation Warp Speed. When using these models, most groups opt to administer the virus intranasally, intratracheal, or intraocular. Often, the “viral shower” approach is common, and it combines all three routes. Researchers at Lovelace used the accumulated volume outcomes with inhalation. Dr. McDonald also mentioned that the primates do not show much pathogenesis, there were no changes in body weight, CT scans, and there were minor pulmonary lesions. This model of COVID-19 is more of a mild inflammatory model. Furthermore, the virus cleared rapidly in primates.
Selection criteria for Animal Models of SARS-CoV-2 Infection
- The animal model has the ACE2 receptor allowing for the virus to bind (permissiveness of infection)
- Ability for viral replication, and the magnitude and distribution of the virus
- Disease severity and symptoms like clinical signs
- Characteristics of immune response
- Anatomical and physiological similarities to human
- Size, availability, and cost
Many pharmaceutical companies are establishing proof-of-concept with systemically administered drugs and are now moving to inhaled formulations. Inhaled therapies offer distinct advantages over other drug administration routes. Some key benefits are ease of use and low level of invasiveness, since they involve direct delivery and high local concentration to the target site. SCIREQ’s intervention platform, the inExpose, offers a significant positive impact on study reproducibility and research efficiency by ensuring process standardization. Integrated with the Aeroneb nebulizer, the inExpose provides sophisticated computer control which enables automated, precise, and repeatable aerosol exposure sessions to small laboratory animals.