Rapid adaption of SARS-CoV-2 in BALB/c mice: Novel mouse model for vaccine efficacy

Authors: Gu et al

Link to paper: https://www.biorxiv.org/content/10.1101/2020.05.02.073411v1.full.pdf

Journal/ Pre-Print: bioRxiv

Key Words: vaccine, animal model, SARS-CoV2

Research Highlights 

1. Creation and characterisation of a murine model of SARS-CoV2 for study of immune response and vaccine efficacy

2. Characterisation of the immune response observed in the model and comparison of young and adult mice

3. Testing of an RBD-based vaccine to show model use

Summary 

Gu et al established a mouse model of SARS-CoV-2 using a mouse-adapted SARS-CoV-2 strain, which they generated through passaging the original SARS-CoV-2 in BALB/c mice. They characterised the immune response and histological damage in both young and adult mice, which had features resembling human disease. Furthermore, they used this animal model to evaluate the efficacy of a receptor binding domain (RBD)-based vaccine they developed. The authors propose that their mouse model can be used to characterise the host immune response towards the virus and to test efficacy and safety of vaccines/therapeutics.

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19: they characterised the cytokine and chemokine response to murine SARS-CoV-2 using a Luminex assay

Understand the virology and/or cell biology of SARS-CoV2/COVID19: they analyse the mutations of the mouse-adapted SARS-CoV2

Develop a vaccine for SARS-CoV2/COVID19: they develop an RBD based vaccine which they test in their mouse model

Develop an animal model for SARS-CoV-2 infection

Study Type

· In vivo study (mouse)

Strengths and limitations of the paper

Novelty: They created a murine model using WT mice in order to study the immune response to SARS-CoV-2 and test vaccine efficacy

Standing in the field: First reported small animal model for SARS-CoV-2

Appropriate statistics: Yes

Viral model used: Original strain was used and passaged 6 times in Balb/c mice to get mouse-adapted human strain

Translatability: They established a mouse model which bears many similarities to human disease, but as is with all mouse models, the question remains whether the findings in mice can be fully translated to human disease.

Main limitations: The vaccine was designed for human SARS-CoV-2 and targets the RBD region (which was mutated in the murine strain). Since the RBD region is key to how the virus can infect mice/humans, it remains to be answered whether this vaccine could be protective in humans. They also characterised the immune response in young and adult mice, neglecting that there was a significant difference in histological score in the lungs. The immune system is very different between mouse and human and therefore the translatability of findings in the model are unknown. The model is probably not easily established by other laboratories as there is no system to amplify the modified virus. There is no guarantee that one would get the same modified virus after 6 passages in a second cohort of Balb/C mice.