A lethal mouse model for evaluating vaccine-associated enhanced respiratory disease during SARS-CoV-2 infection.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34995117.
- Also identified by DOI 10.1126/sciadv.abh3827 and PMC identifier 8741184.
- Licence recorded as CC BY-NC.
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Abstract
One safety concern during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine development has been the vaccine-associated enhanced disease, which is characterized by eosinophilic immunopathology and T helper cell type 2 (T<sub>H</sub>2)–biased immune responses with insufficient neutralizing antibodies. In this study, we established a lethal animal model using BALB/c mice and a mouse-passaged isolate (QHmusX) from a European lineage of SARS-CoV-2. The QHmusX strain induced acute respiratory illness, associated with diffuse alveolar damage and pulmonary edema, in T<sub>H</sub>2-prone adult BALB/c mice, but not in young mice or T<sub>H</sub>1-prone C57BL/6 mice. We also showed that immunization of adult BALB/c mice with recombinant spike protein without appropriate adjuvant caused eosinophilic immunopathology with T<sub>H</sub>2-shifted immune response and insufficient neutralizing antibodies after QHmusX infection. This lethal mouse model is useful for evaluating vaccine-associated enhanced respiratory disease during SARS-CoV-2 infection and may provide new insights into the disease pathogenesis of SARS-CoV-2.