Antiviral efficacy against and replicative fitness of an XBB.1.9.1 clinical isolate
Ryuta Uraki,
Mutsumi Ito,
Maki Kiso,
Seiya Yamayoshi,
Kiyoko Iwatsuki-Horimoto,
Yuko Sakai-Tagawa,
Masaki Imai,
Michiko Koga,
Shinya Yamamoto,
Eisuke Adachi,
Makoto Saito,
Takeya Tsutsumi,
Amato Otani,
Shuetsu Fukushi,
Shinji Watanabe,
Tadaki Suzuki,
Tetsuhiro Kikuchi,
Hiroshi Yotsuyanagi,
Ken Maeda,
Yoshihiro Kawaoka
Affiliations
Ryuta Uraki
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan
Mutsumi Ito
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Maki Kiso
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Seiya Yamayoshi
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan
Kiyoko Iwatsuki-Horimoto
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Yuko Sakai-Tagawa
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Masaki Imai
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan
Michiko Koga
Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of The Institute of Medical Science, University of Tokyo, Tokyo, Japan; Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Shinya Yamamoto
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Eisuke Adachi
Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of The Institute of Medical Science, University of Tokyo, Tokyo, Japan
Makoto Saito
Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of The Institute of Medical Science, University of Tokyo, Tokyo, Japan; Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Takeya Tsutsumi
Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of The Institute of Medical Science, University of Tokyo, Tokyo, Japan; Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Amato Otani
Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of The Institute of Medical Science, University of Tokyo, Tokyo, Japan
Shuetsu Fukushi
National Institute of Infectious Diseases, Tokyo, Japan
Shinji Watanabe
National Institute of Infectious Diseases, Tokyo, Japan
Tadaki Suzuki
National Institute of Infectious Diseases, Tokyo, Japan
Tetsuhiro Kikuchi
Clinic of Nihon Sumo Kyokai, Tokyo, Japan
Hiroshi Yotsuyanagi
Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of The Institute of Medical Science, University of Tokyo, Tokyo, Japan; Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Ken Maeda
National Institute of Infectious Diseases, Tokyo, Japan
Yoshihiro Kawaoka
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA; The University of Tokyo, Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), Tokyo, Japan; Corresponding author
Summary: The emergence and spread of new SARS-CoV-2 variants with mutations in the spike protein, such as the XBB.1.5 and XBB.1.9.1 sublineages, raise concerns about the efficacy of current COVID-19 vaccines and therapeutic monoclonal antibodies (mAbs). In this study, none of the mAbs we tested neutralized XBB.1.9.1 or XBB.1.5, even at the highest concentration used. We also found that the bivalent mRNA vaccine could enhance humoral immunity against XBB.1.9.1, but that XBB.1.9.1 and XBB.1.5 still evaded humoral immunity induced by vaccination or infection. Moreover, the susceptibility of XBB.1.9.1 to remdesivir, molnupiravir, nirmatrelvir, and ensitrelvir was similar to that of the ancestral strain and the XBB.1.5 isolate in vitro. Finally, we found the replicative fitness of XBB.1.9.1 to be similar to that of XBB.1.5 in hamsters. Our results suggest that XBB.1.9.1 and XBB.1.5 have similar antigenicity and replicative ability, and that the currently available COVID-19 antivirals remain effective against XBB.1.9.1.
