Description Eosinophilic immunopathology was induced by T H 2-shifted immune response and inadequate neutralizing antibody in BALB/c mice. 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 H 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 H 2-prone adult BALB/c mice, but not in young mice or T H 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 H 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.
【초록키워드】 neutralizing antibody, SARS-CoV-2, Vaccine development, coronavirus, immune response, Neutralizing antibodies, SARS-COV-2 infection, Infection, animal model, immunopathology, immunization, mice, Respiratory disease, Lineage, Pulmonary edema, Diffuse alveolar damage, Recombinant spike protein, T helper cell, acute respiratory syndrome, acute respiratory illness, BALB/c mice, description, pathogenesis of SARS-CoV-2, C57BL/6, European, caused, the disease, characterized, Eosinophilic, vaccine-associated enhanced disease, 【제목키워드】 SARS-COV-2 infection, Respiratory disease,