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

doi:10.1016/j.isci.2023.108147

Antiviral efficacy against and replicative fitness of an XBB.1.9.1 clinical isolate

iScience. 2023 Oct 4;26(11):108147. doi: 10.1016/j.isci.2023.108147. eCollection 2023 Nov 17.

Authors

Ryuta Uraki^{1

2}, Mutsumi Ito¹, Maki Kiso¹, Seiya Yamayoshi^{1

2}, Kiyoko Iwatsuki-Horimoto¹, Yuko Sakai-Tagawa¹, Masaki Imai^{1

2}, Michiko Koga^{3

4}, Shinya Yamamoto^{1

4}, Eisuke Adachi³, Makoto Saito^{3

4}, Takeya Tsutsumi^{3

4}, Amato Otani³, Shuetsu Fukushi⁵, Shinji Watanabe⁵, Tadaki Suzuki⁵, Tetsuhiro Kikuchi⁶, Hiroshi Yotsuyanagi^{3

4}, Ken Maeda⁵, Yoshihiro Kawaoka^{1

2

7

8}

Affiliations

¹ Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
² The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan.
³ Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
⁴ Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
⁵ National Institute of Infectious Diseases, Tokyo, Japan.
⁶ Clinic of Nihon Sumo Kyokai, Tokyo, Japan.
⁷ Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
⁸ The University of Tokyo, Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), Tokyo, Japan.

Abstract

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.

Keywords: Clinical microbiology; Virology.

Grants and funding

75N93021C00014/AI/NIAID NIH HHS/United States