SARS-CoV-2 Bearing a Mutation at the S1/S2 Cleavage Site Exhibits Attenuated Virulence and Confers Protective Immunity
Michihito Sasaki, Shinsuke Toba, Yukari Itakura, Herman M. Chambaro, Mai Kishimoto, Koshiro Tabata, Kittiya Intaruck, Kentaro Uemura, Takao Sanaki, Akihiko Sato, William W. Hall, Yasuko Orba, Hirofumi Sawa
Abstract
SARS-CoV-2 uses its spike protein to enter target cells. The spike protein is cleaved by a host protease, and this event facilitates viral entry and broadens cell tropism. In this study, we employed SARS-CoV-2 mutants lacking the S protein cleavage site and characterized their growth and pathogenicity using hamsters, a laboratory animal model for SARS-CoV-2 infection. These mutants exerted low pathogenicity but induced sufficient levels of neutralizing antibodies in hamsters, which protected hamsters from rechallenge with pathogenic clinical SARS-CoV-2 strains. These virus mutants may be used as protective immunogens against SARS-CoV-2 infection.