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Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
Distinct sensitivities to SARS-CoV-2 variants in vaccinated humans and mice
Alexandra C Walls1, Laura A VanBlargan2, Kai Wu3
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Abstract:
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has led to the development of a large number of vaccines, several of which are now approved for use in humans. Understanding vaccine-elicited antibody responses against emerging SARS-CoV-2 variants of concern (VOCs) in real time is key to inform public health policies. Serum neutralizing antibody titers are the current best correlate of protection from SARS-CoV-2 challenge in non-human primates and a key metric to understand immune evasion of VOCs. We report that vaccinated BALB/c mice do not recapitulate faithfully the breadth and potency of neutralizing antibody responses elicited by various vaccine platforms against VOCs, compared with non-human primates or humans, suggesting caution should be exercised when interpreting data obtained with this animal model.
Insights
Vaccinated mice do not accurately reflect human antibody responses to SARS-CoV-2 variants. Caution is advised when using mouse models to study vaccine effectiveness against COVID-19 variants of concern.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted rapid vaccine development.
- Understanding immune responses to emerging SARS-CoV-2 variants of concern (VOCs) is crucial for public health.
- Neutralizing antibody titers are key indicators of protection and immune evasion.
Purpose of the Study:
- To evaluate the utility of the BALB/c mouse model in recapitulating human vaccine-elicited antibody responses against SARS-CoV-2 VOCs.
- To compare antibody responses in vaccinated mice with those observed in humans and non-human primates.
Main Methods:
- Vaccination of BALB/c mice with various SARS-CoV-2 vaccine platforms.
- Assessment of serum neutralizing antibody titers against SARS-CoV-2 VOCs.
- Comparison of mouse antibody responses with existing data from human and non-human primate studies.
Main Results:
- BALB/c mice did not faithfully replicate the breadth and potency of neutralizing antibody responses seen in humans or non-human primates.
- The mouse model showed limitations in modeling the immune response to diverse SARS-CoV-2 VOCs.
Conclusions:
- The BALB/c mouse model may not be a reliable correlate for human vaccine-elicited antibody responses against SARS-CoV-2 VOCs.
- Researchers should exercise caution when interpreting data from mouse models regarding vaccine effectiveness and immune evasion in the context of COVID-19.

