Scientists at La Jolla Institute for Immunology (LJI) and Charles River Laboratories International are launching a new project to uncover how different cells in the human immune system respond to SARS-CoV-2, the virus that causes Covid-19.
This new mouse model has been engineered to express human ACE2, the receptor that SARS-CoV-2 uses to infect human cells, and include the same immune cells made by the human body. The work at LJI will be led by Dr Sujan Shresta, a member of the LJI Center for Infectious Disease and Vaccine Research. She explains that these mice may give us a window into Covid-19 that we cannot get in human studies.
Researchers have found that the incubation period for SARS-CoV-2 is usually four to five days. For severe cases, patients tend to show signs of the disease for 10 to 12 days before they are hospitalised. Shresta’s lab will be working closely with Dr Kenneth Kim, Director of the LJI Histopathology Core. He explains that at the time of hospitalisation, people have already been infected for two weeks.
The Shresta Lab will investigate how susceptible these mice are to SARS-CoV-2. The researchers will also measure viral loads in the mice and analyze lung tissues with help from the LJI Histopathology Core.
The goal for Charles River’s Research Model and Services business was to obtain and develop a model to solve the problem of understanding the role of human immune cells in early, acute SARS-CoV-2 infection. The best solution was to increase the susceptibility of the NCG mouse model, which is capable to be immuno-humanised, by engineering human ACE2 receptor (known now to be the receptor of many variant strains of SARS-COV-2) into the mouse ACE2 locus of NCG, named hACE2-NCG(1) leading to a scientific partnership and collaboration with Dr. Shresta’s lab to better define the utility of the model and to understand better mechanisms of early infection in a immuno-humanised mouse.
“With human patients, we can only look at the immune response after there have been signs of infection,” Shresta said. “So we need these animal models to understand the early time points in infection and get a window into the human immune response in tissues such as the lungs.
“I’m really excited about this collaboration. This brand new mouse model is a tremendous opportunity for my lab to study the human immune response on a timescale which is just not possible with clinical studies.”
“We were fortunate to be able to work with Dr. Shresta’s lab. Her lab is well known for its reputation as a persistent and relentless team committed to understanding emerging infectious diseases using mouse models”, said Dr. Steve Festin, Senior Director of Scientific and Commercial Development at Charles River.