Antibody evasiveness of SARS-CoV-2 subvariants KP.3.1.1 and XEC
Qian Wang,
Yicheng Guo,
Ian A. Mellis,
Madeline Wu,
Hiroshi Mohri,
Carmen Gherasim,
Riccardo Valdez,
Lawrence J. Purpura,
Michael T. Yin,
Aubree Gordon,
David D. Ho
Affiliations
Qian Wang
Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Pandemic Research Alliance Unit at the Wu Center for Pandemic Research, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
Yicheng Guo
Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
Ian A. Mellis
Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
Madeline Wu
Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
Hiroshi Mohri
Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
Carmen Gherasim
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
Riccardo Valdez
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
Lawrence J. Purpura
Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
Michael T. Yin
Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
Aubree Gordon
Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA
David D. Ho
Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Pandemic Research Alliance Unit at the Wu Center for Pandemic Research, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Department of Microbiology and Immunology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Corresponding author
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread, and it remains critical to understand the functional consequences of mutations in dominant viral variants. The recombinant JN.1 subvariant XEC recently replaced KP.3.1.1 to become the most prevalent subvariant worldwide. Here, we measure the in vitro neutralization of KP.3.1.1 and XEC by human sera, monoclonal antibodies, and the soluble human ACE2 (hACE2) receptor relative to the parental subvariants KP.3 and JN.1. KP.3.1.1 and XEC are slightly more resistant (1.3- to 1.6-fold) than KP.3 to serum neutralization and antigenically similar. Both also demonstrate greater resistance to neutralization by select monoclonal antibodies and soluble hACE2, all of which target the top of the viral spike. Our findings suggest that the upward motion of the receptor-binding domain in the spike may be partially hindered by the N-terminal domain mutations in KP.3.1.1 and XEC, allowing these subvariants to better evade serum antibodies that target the viral spike in the up position and to have a growth advantage.