A lethal mouse model for evaluating vaccine-associated enhanced respiratory disease during SARS-CoV-2 infection.
Sci Adv, 2022/1/07;8(1):eabh3827.
Iwata-Yoshikawa N[1], Shiwa N[1], Sekizuka T[2], Sano K[1], Ainai A[1], Hemmi T[1, 3], Kataoka M[1], Kuroda M[2], Hasegawa H[4], Suzuki T[1], Nagata N[1]
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PMID: 34995117DOI: 10.1126/sciadv.abh3827
Impact factor: 14.957
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 (TH2)–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 TH2-prone adult BALB/c mice, but not in young mice or TH1-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 TH2-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.
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