A lethal mouse model for evaluating vaccine-associated enhanced respiratory disease during SARS-CoV-2 infection

Naoko Iwata-Yoshikawa; Nozomi Shiwa; Tsuyoshi Sekizuka; Kaori Sano; Akira Ainai; Takuya Hemmi; Michiyo Kataoka; Makoto Kuroda; Hideki Hasegawa; Tadaki Suzuki; Noriyo Nagata

doi:10.1126/sciadv.abh3827

A lethal mouse model for evaluating vaccine-associated enhanced respiratory disease during SARS-CoV-2 infection

Sci Adv. 2022 Jan 7;8(1):eabh3827. doi: 10.1126/sciadv.abh3827. Epub 2022 Jan 7.

Authors

Affiliations

¹ Department of Pathology, National Institute of Infectious Diseases, 208-0011 Tokyo, Japan.
² Pathogen Genomics Center, National Institute of Infectious Diseases, 162-8640 Tokyo, Japan.
³ Department of Biological Science and Technology, Tokyo University of Science, 125-8585 Tokyo, Japan.
⁴ Influenza Virus Research Center, National Institute of Infectious Diseases, 208-0011 Tokyo, Japan.

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_H2)–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_H2-prone adult BALB/c mice, but not in young mice or T_H1-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_H2-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.